Circulation
CLINICAL PRACTICE GUIDELINES
2025 ACC/AHA/ACEP/NAEMSP/SCAI
Guideline for the Management of Patients
With Acute Coronary Syndromes: A Report of
the American College of Cardiology/American
Heart Association Joint Committee on Clinical
Practice Guidelines
Developed in Collaboration With and Endorsed by the American College of Emergency Physicians, National Association of EMS
Physicians, and Society for Cardiovascular Angiography and Interventions
Writing Committee Members*
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Sunil V. Rao, MD, FACC, FSCAI, Chair; Michelle L. O’Donoghue, MD, MPH, FACC, FAHA, Vice Chair;
Marc Ruel, MD, MPH, FACC, FAHA, Vice Chair; Tanveer Rab, MD, FACC, MSCAI, JC Liaison†;
Jaqueline E. Tamis-Holland, MD, FACC, FAHA, FSCAI, JC Liaison†; John H. Alexander, MD, MHS, FACC, FAHA;
Usman Baber, MD, MS, FACC, FSCAI; Heather Baker, EdD‡; Mauricio G. Cohen, MD, FACC, FSCAI;
Mercedes Cruz-Ruiz, CHWI‡; Leslie L. Davis, PhD, RN, ANP-BC, FACC, FAHA; James A. de Lemos, MD, FACC, FAHA;
Tracy A. DeWald, PharmD, MHS, BCPS-AQ Cardiology; Islam Y. Elgendy, MD, FACC, FAHA, FSCAI;
Dmitriy N. Feldman, MD, FACC, FSCAI§; Abhinav Goyal, MD, MHS, FACC, FAHA; Ijeoma Isiadinso, MD, MPH, FACC;
Venu Menon, MD, FACC, FAHA; David A. Morrow, MD, MPH, FACC, FAHA; Debabrata Mukherjee, MD, MS, FACC, FAHA, MSCAI;
Elke Platz, MD, MS, FACEP; Susan B. Promes, MD, MBA, FACEP‖; Sigrid Sandner, MD, MS; Yader Sandoval, MD, FACC, FSCAI;
Rachel Schunder, MA¶; Binita Shah, MD, MS; Jason P. Stopyra, MD, MS#; Amy W. Talbot, MPH¶; Pam R. Taub, MD, FACC;
Marlene S. Williams, MD, FACC**
Aim: The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary
Syndromes” incorporates new evidence since the “2013 ACCF/AHA Guideline for the Management of ST-Elevation
Myocardial Infarction” and the corresponding “2014 AHA/ACC Guideline for the Management of Patients With Non–STElevation Acute Coronary Syndromes” and the “2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary
Intervention for Patients With ST-Elevation Myocardial Infarction.” The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline
for the Management of Patients With Acute Coronary Syndromes” and the “2021 ACC/AHA/SCAI Guideline for Coronary
Artery Revascularization” retire and replace, respectively, the “2016 ACC/AHA Guideline Focused Update on Duration of
Dual Antiplatelet Therapy in Patients With Coronary Artery Disease.”
*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for
detailed information. †ACC/AHA Joint Committee on Clinical Practice Guidelines liaison. ‡Lay stakeholder/patient representative. §Society for Cardiovascular Angiography
and Interventions representative. ‖American College of Emergency Physicians representative. ¶ACC/AHA joint staff representative. #National Association of EMS Physicians representative. **ACC/AHA Joint Committee on Performance Measures representative.
Peer Review Committee Members and AHA/ACC Joint Committee on Clinical Practice Guidelines Members, see page __.
The American Heart Association requests that this document be cited as follows: Rao SV, O’Donoghue ML, Ruel M, Rab T, Tamis-Holland JE, Alexander JH, Morrow
DA, Baber U, Mukherjee D, Baker H, Platz E, Cohen MG, MD, Promes SB, Cruz-Ruiz M, Sandner S, Davis LL, Sandoval Y, de Lemos JA, Schunder R, DeWald TA, Binita
Shah B, Elgendy IY, Stopyra JP, Feldman DN, Talbot AW, Goyal A, Taub PR, Isiadinso I, Williams MS, Menon V. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for
the management of patients with acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical
Practice Guidelines. Circulation. 2025;151:e•••–e•••. doi: 10.1161/CIR.0000000000001309
© 2025 by the American College of Cardiology Foundation and the American Heart Association, Inc.
Circulation is available at www.ahajournals.org/journal/circ
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
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CLINICAL STATEMENTS
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2025 Acute Coronary Syndromes Guideline
Methods: A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews
and meta-analyses, and other evidence conducted on human participants were identified that were published in English
from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other
selected databases relevant to this guideline.
Structure: Many recommendations from previously published guidelines have been updated with new evidence, and new
recommendations have been created when supported by published data.
Key Words: AHA Scientific Statements ◼ acute coronary syndrome(s) ◼ angina, unstable ◼ anticoagulants ◼ aspirin ◼ atrial fibrillation
◼ cardiovascular diseases ◼ coronary artery disease ◼ coronary syndrome ◼ emergency medical services ◼ EMS ◼ fibrinolytic agents
◼ hemorrhage ◼ major adverse cardiovascular events ◼ morphine ◼ myocardial infarction ◼ non–ST-segment elevation myocardial infarction
◼ percutaneous coronary intervention ◼ prehospital ◼ revascularization ◼ risk ◼ ST-segment elevation myocardial infarction
◼ time factors ◼ treatment outcome
TABLE OF CONTENTS
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Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
Top Take-Home Messages. . . . . . . . . . . . . . . . . . . . . . eXXX
Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
1.1. Methodology and Evidence Review. . . . eXXX
1.2. Composition of the Writing
Committee. . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
1.3. Guideline Review and Approval. . . . . . . . eXXX
1.4. Scope of the Guideline. . . . . . . . . . . . . . . . eXXX
1.5. Class of Recommendation and
Level of Evidence. . . . . . . . . . . . . . . . . . . . . eXXX
1.6. Abbreviations. . . . . . . . . . . . . . . . . . . . . . . . . eXXX
2. Overview of ACS. . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
2.1. Definition and Classification of ACS . . . eXXX
3. Initial Evaluation and Management of
Suspected ACS. . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
3.1. Initial Assessment of Suspected
ACS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
3.1.1. Prehospital Assessment and
Management Considerations
for Suspected ACS. . . . . . . . . . . . eXXX
3.1.2. Initial In-Hospital Assessment
of Patients With Confirmed or
Suspected ACS. . . . . . . . . . . . . . . eXXX
3.1.3. Risk Stratification Tools for
Patients With STEMI and
NSTE-ACS . . . . . . . . . . . . . . . . . . . eXXX
3.2. Management of Patients Presenting
With Cardiac Arrest. . . . . . . . . . . . . . . . . . . eXXX
4. Standard Medical Therapies for STEMI
and NSTE-ACS . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
4.1. Oxygen Therapy. . . . . . . . . . . . . . . . . . . . . . eXXX
4.2. Analgesics. . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
4.3. Antiplatelet Therapy . . . . . . . . . . . . . . . . . . eXXX
4.3.1. Aspirin. . . . . . . . . . . . . . . . . . . . . . . . eXXX
4.3.2. Oral P2Y12 Inhibitors During
Hospitalization. . . . . . . . . . . . . . . . eXXX
4.3.3. Intravenous P2Y12
Inhibition. . . . . . . . . . . . . . . . . . . . . . eXXX
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5.
6.
7.
8.
4.3.4. Intravenous Glycoprotein
IIb/IIIa Inhibitors. . . . . . . . . . . . . . . eXXX
4.4. Parenteral Anticoagulation. . . . . . . . . . . . eXXX
4.5. Lipid Management. . . . . . . . . . . . . . . . . . . . eXXX
4.6. Beta-Blocker Therapy. . . . . . . . . . . . . . . . . eXXX
4.7. Renin-Angiotensin-Aldosterone
System Inhibitors. . . . . . . . . . . . . . . . . . . . . eXXX
STEMI Management: Reperfusion
Strategies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
5.1. Regional Systems of STEMI Care. . . . . . eXXX
5.2. Reperfusion at PCI-Capable
Hospitals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
5.2.1. PPCI in STEMI. . . . . . . . . . . . . . . . eXXX
5.2.2. Urgent CABG Surgery. . . . . . . . . eXXX
5.3. Reperfusion at Non–PCI-Capable
Hospitals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
5.3.1. Timing and Choice of Agent
for Fibrinolytic Therapy . . . . . . . . eXXX
5.3.2. Coronary Angiography and
PCI After Fibrinolytic
Therapy. . . . . . . . . . . . . . . . . . . . . . . eXXX
NSTE-ACS: Routine Invasive or Selective
Invasive Initial Approach. . . . . . . . . . . . . . . . . . . . . eXXX
6.1. Rationale and Timing for a Routine
Invasive or Selective Invasive
Approach. . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
Catheterization Laboratory Considerations
in ACS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
7.1. Vascular Access Approach for PCI. . . . . eXXX
7.2. Use of Aspiration Thrombectomy. . . . . . eXXX
7.3. Use of Intracoronary Imaging. . . . . . . . . . eXXX
7.4. Management of Multivessel CAD
in ACS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
7.4.1. Management of Multivessel
CAD in STEMI . . . . . . . . . . . . . . . . eXXX
7.4.2. Management of Multivessel
CAD in NSTE-ACS. . . . . . . . . . . . eXXX
Cardiogenic Shock Management. . . . . . . . . . . . eXXX
8.1. Revascularization in ACS With
Cardiogenic Shock . . . . . . . . . . . . . . . . . . . eXXX
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2025 Acute Coronary Syndromes Guideline
8.2.
ACS who are scheduled for an invasive strategy with timing of angiography to be >24 hours,
upstream treatment with clopidogrel or ticagrelor
may be considered to reduce major adverse cardiovascular events.
Dual antiplatelet therapy with aspirin and an oral
P2Y12 inhibitor is indicated for at least 12 months
as the default strategy in patients with ACS who
are not at high bleeding risk. Several strategies
are available to reduce bleeding risk in patients
with ACS who have undergone PCI and require
antiplatelet therapy: (a) in patients at risk for gastrointestinal bleeding, a proton pump inhibitor is
recommended; (b) in patients who have tolerated
dual antiplatelet therapy with ticagrelor, transition to ticagrelor monotherapy is recommended
≥1 month after PCI; or (c) in patients who require
long-term anticoagulation, aspirin discontinuation is recommended 1 to 4 weeks after PCI with
continued use of a P2Y12 inhibitor (preferably
clopidogrel).
High-intensity statin therapy is recommended for
all patients with ACS, and with the option to initiate concurrent ezetimibe. A nonstatin lipid-lowering agent (eg, ezetimibe, evolocumab, alirocumab,
inclisiran, bempedoic acid) is recommended for
patients already on maximally tolerated statin who
have a low-density lipoprotein cholesterol level
of ≥70 mg/dL (1.8 mmol/L). It is reasonable in
this high-risk population to further intensify lipidlowering therapy if the low-density lipoprotein
cholesterol level is 55 to <70 mg/dL (1.4 to <1.8
mmol/L) and patient is already on a maximally tolerated statin.
In patients with non–ST-segment elevation ACS
who are at intermediate or high risk of ischemic
events, an invasive approach with the intent to proceed with revascularization is recommended during
hospitalization to reduce major adverse cardiovascular events. In patients with non–ST-segment elevation ACS who are at low risk of ischemic events,
a routine invasive or selective invasive approach
with further risk stratification is recommended to
help identify those who may require revascularization and to reduce major adverse cardiovascular
events.
Two procedural strategies are recommended in
patients with ACS who are undergoing PCI: (a)
radial approach is preferred over femoral approach
in patients with ACS undergoing PCI to reduce
bleeding, vascular complications, and death; and
(b) intracoronary imaging is recommended to guide
PCI in patients with ACS with complex coronary
lesions.
MCS in Patients With ACS and
Cardiogenic Shock . . . . . . . . . . . . . . . . . . . eXXX
9. ACS Complications. . . . . . . . . . . . . . . . . . . . . . . . . eXXX
9.1. Mechanical Complications. . . . . . . . . . . . . eXXX
9.2. Electrical Complications and
Prevention of Sudden Cardiac
Death After ACS. . . . . . . . . . . . . . . . . . . . . eXXX
9.3. Pericarditis Management After MI . . . . . eXXX
9.4. Management of LV Thrombus
After MI. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
10. In-hospital Issues in the Management of
ACS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
10.1. Cardiac Intensive Care Unit . . . . . . . . . . . eXXX
10.2. Management of Anemia in ACS. . . . . . . eXXX
10.3. Telemetry and Length of Stay. . . . . . . . . eXXX
10.4. Noninvasive Diagnostic Testing
Prior to Hospital Discharge. . . . . . . . . . . . eXXX
10.5. Discharge Planning. . . . . . . . . . . . . . . . . . . eXXX
10.5.1. Patient Education. . . . . . . . . . . . . eXXX
10.5.2. Postdischarge Follow-Up
and Systems of Care
Coordination. . . . . . . . . . . . . . . . . . eXXX
10.5.3. Cardiac Rehabilitation. . . . . . . . . eXXX
11. Discharge: Long-Term Management and
Secondary Prevention. . . . . . . . . . . . . . . . . . . . . . . eXXX
11.1. DAPT Strategies in the First
12 Months Postdischarge. . . . . . . . . . . . . eXXX
11.1.1. Antiplatelet Therapy in
Patients on Anticoagulation
Postdischarge. . . . . . . . . . . . . . . . . eXXX
11.2. Reassessment of Lipid Levels
Postdischarge. . . . . . . . . . . . . . . . . . . . . . . . eXXX
11.3. SGLT-2 Inhibitors and GLP-1
Receptor Agonists. . . . . . . . . . . . . . . . . . . . eXXX
11.4. Use of Chronic Colchicine. . . . . . . . . . . . . eXXX
11.5. Immunization. . . . . . . . . . . . . . . . . . . . . . . . . eXXX
12. Evidence Gaps and Future Directions. . . . . . . . eXXX
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
Appendix 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
Author Relationships With Industry and
Other Entities������������������������������������������������������������� eXXX
Appendix 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . eXXX
Reviewer Relationships With Industry and
Other Entities������������������������������������������������������������� eXXX
TOP TAKE-HOME MESSAGES
1. Dual antiplatelet therapy is recommended for
patients with acute coronary syndromes (ACS).
Ticagrelor or prasugrel is recommended in preference to clopidogrel in patients with ACS who are
undergoing percutaneous coronary intervention
(PCI). In patients with non–ST-segment elevation
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2.
3.
4.
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6. A strategy of complete revascularization is recommended in patients with ST-segment elevation
myocardial infarction or non–ST-segment elevation ACS. The choice of revascularization method
(ie, coronary artery bypass graft surgery versus
multivessel PCI) in non–ST-segment elevation
ACS and multivessel disease should be based on
the complexity of the coronary artery disease and
comorbid conditions. PCI of significant nonculprit
stenoses for patients with ST-segment elevation myocardial infarction can be performed in a
single procedure or staged with some preference
toward performing multivessel PCI in a single
procedure. In patients with ACS and cardiogenic
shock, emergency revascularization of the culprit vessel is indicated; however, routine PCI of
non–infarct-related arteries at the time of PCI is
not recommended.
7. Based on one trial, use of the microaxial flow
pump in selected patients with cardiogenic shock
related to acute myocardial infarction is reasonable to reduce death. However, complications
such as bleeding, limb ischemia, and renal failure
are higher with the microaxial flow pump compared with usual care. Therefore, careful attention to vascular access and weaning of support
is important to appropriately balance the benefits
and risks.
8. Red blood cell transfusion to maintain a hemoglobin of 10 g/dL may be reasonable in patients
with ACS and acute or chronic anemia who are not
actively bleeding.
9. After discharge, focus on secondary prevention is
fundamental. A fasting lipid panel is recommended
4 to 8 weeks after initiating or adjusting the dose
of lipid-lowering therapy. Referral to cardiac rehabilitation is also recommended, with the option
for home-based programs for patients unable or
unwilling to attend in person.
PREAMBLE
Since 1980, the American College of Cardiology (ACC)
and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular
health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide
a foundation for the delivery of quality cardiovascular
care. The ACC and AHA sponsor the development and
publication of clinical practice guidelines without commercial support, and members volunteer their time to
the writing and review efforts. Guidelines are official
policy of the ACC and AHA. For some guidelines, the
ACC and AHA collaborate with other organizations.
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2025 Acute Coronary Syndromes Guideline
Intended Use
Clinical practice guidelines provide recommendations
applicable to patients with or at risk of developing
cardiovascular disease (CVD). The focus is on medical practice in the United States, but these guidelines
are relevant to patients throughout the world. Although
guidelines may be used to inform regulatory or payer
decisions, the intent is to improve quality of care and
align with patients’ interests. Guidelines are intended to
define practices meeting the needs of patients in most,
but not all, circumstances and should not replace clinical judgment.
Clinical Implementation
Management, in accordance with guideline recommendations, is effective only when followed by both
practitioners and patients. Adherence to recommendations can be enhanced by shared decision-making
between clinicians and patients, with patient engagement in selecting interventions on the basis of individual values, preferences, and associated conditions
and comorbidities.
Methodology and Modernization
The ACC/AHA Joint Committee on Clinical Practice
Guidelines (Joint Committee) continuously reviews, updates, and modifies guideline methodology on the basis
of published standards from organizations, including the
National Academy of Medicine (formerly the Institute
of Medicine),1 and on the basis of internal reevaluation.
Similarly, presentation and delivery of guidelines are reevaluated and modified in response to evolving technologies and other factors to optimally facilitate dissemination of information to health care professionals at the
point of care.
Numerous modifications to the guidelines have
been implemented to make them shorter and enhance
“user friendliness.” Guidelines are written and presented in a modular, “knowledge chunk” format in
which each chunk includes a table of recommendations, a brief synopsis, recommendation-specific supportive text, and, when appropriate, flow diagrams or
additional tables. Hyperlinked references are provided
for each modular knowledge chunk to facilitate quick
access and review.
In recognition of the importance of cost–value considerations, in certain guidelines, when appropriate and
feasible, an assessment of value for a drug, device, or
intervention may be performed in accordance with the
ACC/AHA methodology.2
To ensure that guideline recommendations remain
current, new data will be reviewed on an ongoing basis
by the writing committee and staff. When applicable,
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
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Selection of Writing Committee Members
The Joint Committee strives to ensure that the guideline writing committee contains requisite content expertise and is representative of the broader cardiovascular community by selection of experts across
a spectrum of backgrounds, representing different
geographic regions, sexes, races, ethnicities, intellectual perspectives/biases, and clinical practice settings.
Organizations and professional societies with related
interests and expertise are invited to participate as
collaborators.
Relationships With Industry and Other Entities
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The ACC and AHA have rigorous policies and methods
to ensure that documents are developed without bias or
improper influence. The complete policy on relationships
with industry and other entities (RWI) can be found at
https://www.acc.org/guidelines/about-guidelines-andclinical-documents/relationships-with-industry-policy.
Appendix 1 of the guideline lists writing committee members’ comprehensive and relevant RWI; for the purposes
of full transparency, comprehensive and relevant disclosure information for the Joint Committee is also available
at
https://www.acc.org/guidelines/about-guidelinesand-clinical-documents/guidelines-and-documentstask-forces.
Evidence Review and Evidence Review
Committees
In developing recommendations, the writing committee uses evidence-based methodologies that are
based on all available data.3,4 Literature searches focus on randomized controlled trials (RCTs) but also
include registries, nonrandomized comparative and
descriptive studies, case series, cohort studies, systematic reviews, and expert opinion. Only key references are cited.
An independent evidence review committee is commissioned when there are ≥1 questions deemed of
utmost clinical importance and merit formal systematic
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
review to determine which patients are most likely to
benefit from a drug, device, or treatment strategy, and
to what degree. Criteria for commissioning an evidence
review committee and formal systematic review include
absence of a current authoritative systematic review,
feasibility of defining the benefit and risk in a time frame
consistent with the writing of a guideline, relevance to a
substantial number of patients, and likelihood that the
findings can be translated into actionable recommendations. Evidence review committee members may include
methodologists, epidemiologists, clinicians, and biostatisticians. Recommendations developed by the writing
committee on the basis of the systematic review are
marked “SR.”
Guideline-Directed Medical Therapy
The term guideline-directed medical therapy encompasses clinical evaluation, diagnostic testing, and both
pharmacological and procedural treatments. For these
and all recommended drug treatment regimens, the
reader should confirm dosage with product insert material and evaluate for contraindications and interactions.
Recommendations are limited to drugs, devices, and
treatments approved for clinical use in the United States.
Catherine M. Otto, MD, FACC, FAHA
Chair, ACC/AHA Joint Committee on
Clinical Practice Guidelines
1. INTRODUCTION
1.1. Methodology and Evidence Review
The recommendations listed in this guideline are,
whenever possible, evidence based. An initial extensive evidence review—which included literature derived from research involving human subjects, published in English, and indexed in MEDLINE (through
PubMed), EMBASE, the Cochrane Library, the Agency
for Healthcare Research and Quality, and other selected databases relevant to this guideline—was conducted from July 2023 to April 2024. Key search words
included but were not limited to the following: AHA/
ACC Clinical Practice Guidelines; acute coronary
syndrome(s); angina, unstable; anticoagulants; aspirin; atrial fibrillation; cardiovascular diseases; coronary
artery disease (CAD); coronary syndrome; emergency
medical services; fibrinolytic agents; hemorrhage; major adverse cardiovascular events (MACE); morphine;
myocardial infarction; non–ST-elevation myocardial
infarction (NSTEMI); percutaneous coronary intervention (PCI); prehospital; revascularization; risk; STelevation myocardial infarction (STEMI); time factors;
treatment outcome.
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recommendations will be updated with new evidence, or
new recommendations will be created when supported
by published evidence-based data. Going forward, targeted sections/knowledge chunks will be revised
dynamically after publication and timely peer review
of potentially practice-changing science. The previous
designations of “full revision” and “focused update” have
been phased out. For additional information and policies on guideline development, readers may consult the
ACC/AHA guideline methodology manual3 and other
methodology articles.4–6
2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
Rao et al
Additional relevant studies, which were published
through April 2024 during the guideline writing process, were also considered by the writing committee
and added to the evidence tables when appropriate.
The final evidence tables summarize the evidence
used by the writing committee to formulate recommendations. References selected and published in
the present document are representative and not allinclusive.
1.2. Composition of the Writing Committee
The writing committee consisted of general cardiologists,
interventional cardiologists, cardiovascular surgeons,
critical care cardiologists, emergency physicians, cardiac imaging experts, advanced practice nurses, clinical
pharmacists, and lay/patient representatives. The writing
committee included representatives from the AHA, ACC,
American College of Emergency Physicians (ACEP), National Association of EMS Physicians (NAEMSP), and
Society for Cardiovascular Angiography and Interventions (SCAI). Appendix 1 of the current document lists
writing committee members’ comprehensive and relevant RWI.
1.3. Guideline Review and Approval
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The Joint Committee appointed a peer review committee to review the document. The peer review committee
comprised individuals nominated by the ACC, AHA, and
the collaborating organizations. Reviewers’ RWI information was distributed to the writing committee and is
published in this document (Appendix 2). This document
was approved for publication by the governing bodies
of the ACC and the AHA and was endorsed by ACEP,
NAEMSP, and SCAI.
1.4. Scope of the Guideline
The scope of the “2025 ACC/AHA/ACEP/NAEMSP/
SCAI Guideline for the Management of Patients With
Acute Coronary Syndromes” (referred to hereafter as
the “2025 ACS guideline”) is to incorporate new evidence since the publication of the “2013 ACCF/AHA
Guideline for the Management of ST-Elevation Myocardial Infarction,”1 the corresponding “2014 AHA/ACC
Guideline for the Management of Patients With Non–
ST-Elevation Acute Coronary Syndromes,”2 and the
“2015 ACC/AHA/SCAI Focused Update on Primary
Percutaneous Coronary Intervention for Patients With
ST-Elevation Myocardial Infarction.”3 The 2025 ACS
guideline and the “2021 ACC/AHA/SCAI Guideline for
Coronary Artery Revascularization”4 retire and replace,
respectively, the “2016 ACC/AHA Guideline Focused
Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease.”5 This guideline
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2025 Acute Coronary Syndromes Guideline
primarily focuses on the management of type 1 acute
myocardial infarction (AMI). It can be challenging to differentiate type 1 versus type 2 MI. In cases of uncertainty and depending on the benefits/risks of a specific
diagnostic or therapeutic intervention, it may be appropriate to err on the side of considering an event a type 1
acute coronary syndrome (ACS) event until established
to be otherwise.
In the United States, an estimated 805 000 AMIs
occur annually of which 605 000 are first MI events and
200 000 are recurrent.6–8 Although significant morbidity
and mortality are associated with MI, 30-day and in-hospital mortality rates after ST-segment elevation myocardial infarction (STEMI) have declined in part as a result
of timely reperfusion and implementation of evidencebased secondary prevention.9 From 2011 to 2021 in the
United States, the annual death rate attributable to coronary heart disease declined by 15.0%.6 The economic
impact of MI is also substantial, with the total annual
cost estimated at $84.9 billion, including direct medical
expenditures and indirect lost productivity and wages.10,11
The incidence of MI is higher among Black males compared with non-Hispanic White males for reasons that
are believed to be multifactorial.12,13 Potential factors
that may contribute to this disparity include a higher
prevalence of risk factors for CAD, less use of guidelinerecommended medications post-MI, and socioeconomic
factors.14–19 In addition to racial disparities, there are
sex-related disparities in the prevalence, presentation,
treatment, and outcomes of ACS even after adjusting
for confounding factors such as income, geography, and
education.20 Women tend to present with ACS on average 10 years later than men and with a greater burden
of CVD risk factors. Although chest pain remains the
most common symptom of AMI, women are more likely
than men to present with accompanying non–chest pain
symptoms.21–24 A delay in recognition of these symptoms can result in delays in presentation, diagnosis,
and timely treatment of women with ACS. Studies have
also shown that women presenting with ACS are less
likely to be correctly diagnosed with an ACS, receive
guideline-directed medical therapy,25–27 and/or undergo
coronary revascularization when indicated.28,29 Bridging
these racial and sex gaps will require continued provider
education, better understanding of barriers to accessing quality care and guideline-directed medical therapy,
and changes at the community and legislative level to
address social determinants of health such as income,
employment status, neighborhood safety, and access to
healthy foods.
In developing the 2025 ACS guideline, the writing
committee reviewed previously published guidelines
and related scientific statements. Table 1 contains a
list of these publications deemed pertinent to this writing effort. It is intended for use as a resource, obviating
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Table 1. Associated Publications
Publication Year
(Reference)
Organization
Guidelines
Management of blood cholesterol
AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/
AGS/APhA/ASPC/NLA/PCNA
201830
Prevention, detection, evaluation, and management of high blood pressure in adults
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/
ASH/ASPC/NMA/PCNA
201831
Primary prevention of cardiovascular disease
ACC/AHA
201932
Coronary artery revascularization
ACC/AHA/SCAI
20214
Evaluation and diagnosis of chest pain
AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR
202133
Prevention of stroke in patients with stroke and transient ischemic attack
AHA/ASA
202134
Management of heart failure
AHA/ACC/HFSA
202235
Management of patients with chronic coronary disease
AHA/ACC/ACCP/ASPC/NLA/PCNA
202336
Diagnosis and management of atrial fibrillation
ACC/AHA/ACCP/HRS
202337
Home-based cardiac rehabilitation
AHA/ACC/AACVPR
201938
Classification of cardiogenic shock
SCAI, endorsed by ACC/AHA/SCCM/STS
201939
Contemporary diagnosis and management of patients with myocardial infarction in the
absence of obstructive coronary artery disease
AHA
201940
Invasive management of acute myocardial infarction complicated by cardiogenic shock
AHA
202141
Mechanical complications of acute myocardial infarction
AHA
202142
SHOCK stage classification update
SCAI, endorsed by ACC/ACEP/AHA/ESC/
ACVC/ISHLT/ SCCM/STS
202143
Management of patients at risk for and with left ventricular thrombus
AHA
202244
Cardiac catheterization laboratory management of the comatose adult patient with an
out-of-hospital cardiac arrest
AHA
202445
Other Relevant Documents
Downloaded from http://ahajournals.org by on February 28, 2025
AACVPR indicates American Association of Cardiovascular and Pulmonary Rehabilitation; AAPA, American Academy of Physician Associates (formerly American Academy of Physician Assistants); ABC, Association of Black Cardiologists; ACC, American College of Cardiology; ACCP, American College of Clinical
Pharmacy; ACEP, American College of Emergency Physicians; ACPM, American College of Preventive Medicine; ACVC, Association for Acute Cardiovascular
Care; ADA, American Diabetes Association; AGS, American Geriatrics Society; AHA, American Heart Association; APhA, American Pharmacists Association;
ASA, American Stroke Association; ASCVD, atherosclerotic cardiovascular disease; ASE, American Society of Echocardiography; ASH, American Society of
Hypertension; ASPC, American Society for Preventive Cardiology; CHEST, American College of Chest Physicians; ESC, European Society of Cardiology; HFSA,
Heart Failure Society of America; HRS, Heart Rhythm Society; ISHLT, International Society for Heart and Lung Transplantation; NLA, National Lipid Association;
NMA, National Medical Association; PCNA, Preventive Cardiovascular Nurses Association; SAEM, Society for Academic Emergency Medicine; SCAI, Society for
Cardiovascular Angiography and Interventions; SCCM, Society of Critical Care Medicine; SCCT, Society of Cardiovascular Computed Tomography; SCMR, Society
for Cardiovascular Magnetic Resonance; SHOCK, Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock trial; and STS, Society of
Thoracic Surgery.
the need to repeat existing guideline recommendations.
Some recommendations have been carried forward
from previously published guidelines. If unchanged,
those recommendations remain current. Any changes
to the formatting or content of these recommendations
are defined as:
• Modified: formatting changes (eg, minor verbiage
modifications such as PICO[TS] structure)
• Adapted: substantive changes (eg, major adaptations, such as a change in Class of Recommendation
[COR], Level of Evidence [LOE], drug, or device
classification).
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Changes are depicted in a footnote below the recommendation tables.
1.5. Class of Recommendation and Level of
Evidence
The COR indicates the strength of recommendation, encompassing the estimated magnitude and certainty of
benefit in proportion to risk. The LOE rates the quality
of scientific evidence supporting the intervention on the
basis of the type, quantity, and consistency of data from
clinical trials and other sources (Table 2).1
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AND GUIDELINES
Title
CLINICAL STATEMENTS
AND GUIDELINES
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Table 2. Applying the American College of Cardiology/American Heart Association Class of Recommendation and Level of
Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* (Updated May 2019)
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1.6. Abbreviations
Abbreviation
Meaning/Phrase
Abbreviation
Meaning/Phrase
CDP
clinical decision pathway
CICU
cardiac intensive care unit
ACEi
angiotensin-converting enzyme inhibitor
ACS
acute coronary syndromes
CR
cardiac rehabilitation
AF
atrial fibrillation
cTn
cardiac troponin
AMI
acute myocardial infarction
CVD
cardiovascular disease
ARB
angiotensin receptor blocker
DAPT
dual antiplatelet therapy
ASCVD
atherosclerotic cardiovascular disease
DOAC
direct oral anticoagulant
CABG
coronary artery bypass grafting
ECG
electrocardiogram
CAD
coronary artery disease
FDA
US Food and Drug Administration
CCD
chronic coronary disease
FFR
fractional flow reserve
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Meaning/Phrase
FMC
first medical contact
GLP-1
glucagon-like peptide-1
HF
heart failure
hs-cTn
high-sensitivity cardiac troponin
IABP
intra-aortic balloon pump
ICD
implantable cardioverter-defibrillator
IVUS
intravascular ultrasound
LDL
low-density lipoprotein
LDL-C
low-density lipoprotein cholesterol
LV
left ventricular
LVEF
left ventricular ejection fraction
MACE
major adverse cardiovascular event
MCS
mechanical circulatory support
MI
myocardial infarction
MINOCA
MI with nonobstructive coronary artery disease
MVD
multivessel disease
NSTE-ACS
non–ST-segment elevation ACS
NSTEMI
non–ST-segment elevation myocardial infarction
OCT
optical coherence tomography
OR
odds ratio
PCI
percutaneous coronary intervention
PCSK9
proprotein convertase subtilisin/kexin type 9
PPCI
primary percutaneous coronary intervention
PPI
proton pump inhibitor
QOL
quality of life
RCT
randomized controlled trial
ROSC
return of spontaneous circulation
SGLT-2
sodium-glucose cotransporter-2
STEMI
ST-segment elevation myocardial infarction
UFH
unfractionated heparin
VA-ECMO
venoarterial extracorporeal membrane oxygenation
2. OVERVIEW OF ACS
2.1. Definition and Classification of ACS
ACS are typically caused by the disruption (rupture or erosion) of an unstable coronary artery atherosclerotic plaque
with associated partial or complete coronary artery thrombosis and/or microemboli, resulting in diminished blood
flow to the myocardium and subsequent myocardial ischemia (Figure 1).1,2 ACS includes 3 related clinical conditions that exist along a continuum of severity: (1) unstable
angina, (2) non–ST-segment elevation myocardial infarction (NSTEMI), and (3) STEMI. The initial diagnosis and
classification of ACS should be based on the clinical history and symptomatology, interpretation of the ECG (Table
3), and assessment of cardiac troponin (cTn). Unstable angina is defined by transient myocardial ischemia leading to
diminished flow in the absence of significant myonecrosis
detected by circulating troponin. In contrast, patients with
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AND GUIDELINES
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Abbreviation
Figure 1. Pathobiology of a Type 1 Myocardial Infarction Due
to Atherosclerotic Plaque Disruption.
Progressive lipid accumulation and inflammation within an
atherosclerotic plaque may lead to plaque instability. Rupture or
erosion of the atherosclerotic plaque and exposure of plaque
contents to the circulation may then culminate in activation of the
coagulation cascade and subsequent thrombosis. When this occurs
in the epicardial vessels of the coronary circulation, the presence
of thrombus may compromise flow to the myocardium, leading to
myocardial ischemia and eventual myonecrosis. Illustration by Patrick
Lane, ScEYEnce Studios. Copyright 2025 American College of
Cardiology Foundation, and American Heart Association, Inc.
more prolonged or severe myocardial ischemia are diagnosed with MI and have elevated biomarkers of myonecrosis. Patients with NSTEMI may have a partially occluded
coronary artery leading to subendocardial ischemia, while
those with STEMI typically have a completely occluded
vessel leading to transmural myocardial ischemia and infarction (Figure 2).3,4 The pathophysiology of ACS can be
dynamic and thus patients can rapidly progress from one
clinical condition (eg, unstable angina, NSTEMI, STEMI) to
another during the course of their presentation and initial
evaluation and treatment. Other, less common causes of
myocardial ischemia, among others, include coronary artery spasm, embolism, and dissection.3
This guideline will focus on the acute management
of ACS, including unstable angina, NSTEMI, and STEMI,
which are presumed to result from atherosclerotic plaque
rupture or plaque erosion and subsequent thrombosis.4
Under the Universal Definition of MI, these MI events
would be classified as type 1 MI events (Table 4).4 The
diagnostic evaluation of chest pain and the management
of type 2 MI, spontaneous coronary artery dissection, and
MINOCA (MI with nonobstructive coronary artery disease)
are covered in separate documents.5–8 A detailed description of the approach to the evaluation of patients with
chest pain can be found in the 2021 AHA/ACC/ASE/
CHEST/SAEM/SCCT/SCMR Chest Pain Guideline.5
Progressive lipid accumulation and inflammation
within an atherosclerotic plaque may lead to plaque
instability.1 Rupture of the atherosclerotic plaque and
exposure of plaque contents to the circulation may then
culminate in activation of the coagulation cascade and
subsequent thrombosis. The presence of thrombus may
compromise flow to the myocardium, leading to myocardial ischemia and eventual myonecrosis. Since early initiation of therapy is imperative for patients with ACS, a
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AND GUIDELINES
Table 3. Electrocardiographic Interpretation for Patients With Suspected Acute Coronary Syndromes
NSTE-ACS
STEMI
Electrocardiographic
evidence of ischemia
New or presumed new and usually dynamic horizontal or downsloping ST-segment depression ≥0.5 mm in ≥2 contiguous leads
and/or T-wave inversion >1 mm in ≥2 contiguous leads with prominent R wave or R/S ratio >1 or transient ST-segment elevation.
New or presumed new ST-elevation of ≥1 mm in ≥2 anatomically
contiguous leads (measured at the J-point) in all leads other than
V2-V3 and ≥2 mm in men ≥40 y, ≥2.5 mm in men <40 y, and
≥1.5 mm in women regardless of age in leads V2-V3.*
Other observed
electrocardiographic
changes
Many patients with NSTE-ACS have either nonspecific ST-segment or T-wave changes or a normal ECG. The absence of electrocardiographic evidence of ischemia does not exclude ACS.
Posterior leads (V7-V9) should be obtained in patients with
suspected left circumflex occlusion particularly in the setting of
isolated ST-segment depression ≥0.5 mm in leads V1-V3.
Adapted with permission from Thygesen et al.4 Copyright 2018 The European Society of Cardiology, American College of Cardiology Foundation, American Heart
Association, Inc., and the World Heart Federation. Adapted from Kontos et al.11 Copyright 2022 American College of Cardiology Foundation.
*ST-segment changes may be observed in other conditions including acute pericarditis, left ventricular hypertrophy, LBBB, Brugada syndrome, right ventricular pacing,
Takotsubo syndrome, and early repolarization that may obscure the diagnosis of STEMI.12 New or presumably new LBBB at presentation occurs infrequently and should
not be considered diagnostic of AMI in isolation; clinical correlation is required.13 A new LBBB in an asymptomatic patient does not constitute a STEMI equivalent.11
ACS indicates acute coronary syndromes; AMI, acute myocardial infarction, LBBB, left bundle branch block; NSTE-ACS, non–ST-segment elevation ACS; and STEMI,
ST-segment elevation MI.
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high index of suspicion is warranted for those who present with signs and symptoms that could be consistent
with myocardial ischemia.
Patients with ACS are at the highest risk for cardiovascular complications acutely, including prior to hospital
presentation and during the early hospital phase. With
appropriate management, this risk begins to attenuate;
however, patients remain at increased risk of recurrent
cardiovascular events for several months to years after
an ACS.9 This may in part be related to the acute inflammatory milieu that exists after ACS that may contribute to
a heightened risk of recurrent events. Although the point
at which a patient transitions from being a patient with an
acute ACS to one with more stable or chronic coronary
disease (CCD) is incompletely defined, many of the medications indicated at discharge in patients with an ACS
are similar to those for the management of a patient with
CCD and should be extended more than a year beyond
ACS. The long-term management of patients with ACS
who are presumed to now have more stable coronary
disease has been described in the 2023 AHA/ACC/
ACCP/ASPC/NLA/PCNA Chronic Coronary Disease
Guideline.10
3. INITIAL EVALUATION AND
MANAGEMENT OF SUSPECTED ACS
3.1. Initial Assessment of Suspected ACS
3.1.1. Prehospital Assessment and Management
Considerations for Suspected ACS
Recommendations for Prehospital Assessment and Management
Considerations for Suspected ACS
Referenced studies that support recommendations are summarized
in the Evidence Table.
COR
LOE
Recommendations
Suspected ACS
1
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B-NR
1. In patients with suspected ACS, a 12-lead ECG
should be acquired and interpreted within 10
minutes of first medical contact (FMC)* to identify
patients with STEMI.1,2
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Recommendations for Prehospital Assessment and Management
Considerations for Suspected ACS (Continued)
COR
1
LOE
Recommendations
C-LD
2. In patients with suspected ACS in which the initial
ECG is nondiagnostic of STEMI, serial ECGs to
detect potential ischemic changes should be
performed, especially when clinical suspicion of
ACS is high, symptoms are persistent, or the
clinical condition deteriorates.†3,4
B-NR
3. In patients with suspected STEMI, immediate
emergency medical services (EMS) transport to
a PCI-capable hospital for primary PCI (PPCI‡)
is the recommended triage strategy, with an
FMC–to-first-device time system goal of ≤90
minutes.5–7
B-NR
4. In patients with suspected STEMI, early advance
notification of the receiving PCI-capable hospital
by EMS personnel and activation of the cardiac
catheterization team is recommended to reduce
time to reperfusion.1,8,9
STEMI
1
1
*FMC indicates the time point when the patient is initially assessed by a health
care professional who can obtain and interpret the ECG and deliver initial interventions (eg, defibrillation).
†Modified from the “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR
Guideline for the Evaluation and Diagnosis of Chest Pain.”10
‡PPCI refers to emergency PCI in the setting of STEMI to achieve reperfusion
in patients without previous fibrinolytic treatment.
Synopsis
Rapid and coordinated prehospital care plays a critical
role in the optimal management of patients with suspected ACS.11 Patients with suspected ACS should
be transported to the emergency department (ED)
by emergency medical services (EMS).12 In contrast
to transport by private vehicle, EMS transport allows
for assessment, monitoring, and treatment of potentially life-threatening conditions such as arrhythmias
or cardiac arrest during transport to the ED.13 In patients with suspected ACS, trained prehospital personnel should obtain a focused history and physical
examination (including assessment of vital signs) and
obtain at least one 12-lead ECG so that the electrocardiographic findings can facilitate next steps in
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Figure 2. Types and Classification of Acute Coronary Syndromes.
NSTEMI indicates non–ST-segment elevation myocardial infarction; and STEMI, ST-segment elevation myocardial infarction.
Illustration by Patrick Lane, ScEYEnce Studios. Copyright 2025 American College of Cardiology Foundation, and the American Heart
Association, Inc.
patient triage. Specifically, patients should be managed based on the presence or absence of ST-segment elevation (or suspected equivalent) on the 12lead ECG (Table 3 for STEMI electrocardiographic
criteria). When possible, electrocardiographic tracings
can be transmitted to the PPCI center while en route
to help expedite coronary reperfusion upon arrival. Because patients with ACS and evidence of heart failure
(HF), ventricular arrhythmias, or cardiogenic shock in
the prehospital setting are at highest risk for death,
identification of these complications is important with
subsequent triage of these patients to a PCI-capable
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facility when possible (Section 8, “Cardiogenic Shock
Management”).14,15
Recommendation-Specific Supportive Text
1. The early acquisition and recording of prehospital
12-lead ECGs by trained personnel is associated
with shorter reperfusion times and lower mortality rates from STEMI if this diagnostic information
is integrated in patients’ care.1,2,16 Appropriately
trained EMS personnel (ie, paramedics) can interpret 12-lead ECGs for the identification of STEMI
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AND GUIDELINES
Table 4. Types of Acute Myocardial Infarction According to the Universal Definition of Myocardial Infarction
Type 1*
Caused by acute coronary atherothrombosis, usually precipitated by atherosclerotic plaque disruption (rupture or erosion) and
often associated with partial or complete vessel thrombosis.
Type 2
Caused by an imbalance between myocardial oxygen supply and demand unrelated to acute coronary atherothrombosis.
Type 3
Cardiac death, with symptoms of myocardial ischemia and presumed ischemic electrocardiographic changes or ventricular arrythmia, before blood
samples for cardiac biomarkers can be obtained or increases in cardiac biomarkers can be identified and/or in whom MI is identified by autopsy.
Type 4
4a: Peri-PCI MI caused by a procedural complication and detected ≤48 h after PCI.
4b: Post-PCI MI caused by coronary stent or stent scaffold thrombosis.
4c: Post-PCI MI caused by coronary stent restenosis.
Type 5
Peri-CABG MI caused by a procedural complication detected ≤48 h after CABG surgery.
Adapted with permission from Thygesen et al.4 Copyright 2018 The European Society of Cardiology, American College of Cardiology Foundation, American Heart
Association, Inc., and the World Heart Federation.
*This guideline focuses on the management of type 1 AMI. The diagnostic evaluation of chest pain and the management of type 2 MI, SCAD, and MINOCA are covered
in separate documents.5–8
AMI indicates acute myocardial infarction; CABG, coronary artery bypass grafting; MI, myocardial infarction; MINOCA, MI with nonobstructive coronary artery disease;
PCI, percutaneous coronary intervention; and SCAD, spontaneous coronary artery dissection.
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with high accuracy.17 When ST-segment elevation
or an equivalent finding is present on the initial ECG
(Table 3), initial management and triage should
follow the prescribed STEMI treatment algorithm.
Electrocardiographic changes are not required to
confirm a diagnosis of non–ST-segment elevation
ACS (NSTE-ACS).
2. In patients for whom the initial ECG is nondiagnostic, serial ECGs should be performed during transport to the hospital especially when clinical suspicion
of ACS is high, ischemic symptoms are persistent,
or the clinical condition deteriorates.3,4 Acquisition
of subsequent ECGs should not delay transport to
a hospital. A second and/or third ECG during EMS
transport may identify up to 15% of additional STEMI
cases not present on the first ECG.3 In an observational study of 728 patients with suspected ACS
who underwent serial prehospital ECGs, a STEMI
diagnosis was subsequently made in 8% of patients
following an initial nondiagnostic ECG with a median
of 12 minutes after the first study.4 Posterior ECG
leads (V7-V9) should be applied in patients with
ongoing symptoms and a nondiagnostic ECG and
those with ST-segment depressions in leads V1-V3
to assess for ST-segment elevation in the posterior
leads, which could indicate a posterior STEMI.
3. PPCI is the preferred method of reperfusion for
patients with STEMI.18 Rapid reperfusion of the
infarct-related artery is associated with improved
myocardial salvage and improved survival.19,20 For
those who are managed by PPCI, each 30 minutes of delay is associated with an increase in the
relative risk of 1-year mortality by 7.5%.19 As such,
evidence supports system-level interventions to
reduce time-to-device.11 Patients with prehospital identification of STEMI should preferentially
be transported to a PCI-capable hospital with
a goal of FMC–to–first-device time of ≤90 minutes.20 For patients who are directly transported to
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the hospital by EMS, the time to treatment goal is
defined as the FMC by EMS until coronary reperfusion. Direct transfer to a PCI-capable facility has
been associated with shorter reperfusion times
and lower mortality compared with transport to the
closest non–PCI-capable hospital.21 In prehospital settings where a FMC–to–first-device goal of
≤90 minutes is not feasible in patients with STEMI,
direct transport to a PCI-capable hospital may be
considered if the anticipated FMC-to-device time
is ≤120 minutes.22,23 See Section 5.1, “Regional
Systems of STEMI Care,” for further details.
4. The implementation of several care processes has
demonstrated significant reductions in reperfusion
times in patients with STEMI when implemented
within a regional medical system.24 These include
(1) prehospital catheterization laboratory activation,
(2) single call transfer protocol for patients from
a non-PCI facility, and (3) ED bypass to transport
patients directly to the catheterization laboratory
for those presenting by EMS to a PCI-capable hospital, and for transfers from other facilities. In particular, the prehospital activation of catheterization
laboratories has been associated with lower shortand long-term mortality in patients presenting with
STEMI.1,8,25 See Section 5.1, “Regional Systems of
STEMI Care,” for further details.
3.1.2. Initial In-Hospital Assessment of Patients With
Confirmed or Suspected ACS
Recommendations for Initial In-Hospital Assessment of Patients With
Confirmed or Suspected ACS
Referenced studies that support recommendations are summarized
in the Evidence Table.
COR
LOE
Recommendations
1
B-NR
1. In patients with suspected ACS, acquisition and
interpretation of an ECG within 10 minutes is
recommended to help guide patient
management.*1,2
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COR
LOE
Recommendations
1
B-NR
2. In patients with suspected ACS in whom the
initial ECG is nondiagnostic, serial 12-lead ECGs
should be performed to detect potential ischemic
changes, especially when clinical suspicion of
ACS is high, symptoms are persistent, or clinical
condition deteriorates.*3
1
B-NR
3. In patients with suspected ACS, cTn should be
measured as soon as possible, preferably using a
high-sensitivity cTn (hs-cTn) assay.*4–7
B-NR
4. In patients with suspected ACS with an initial
hs-cTn or cTn that is nondiagnostic, the
recommended time intervals for repeat
measurements after the initial sample collection
(time zero) are 1 to 2 hours for hs-cTn and 3 to 6
hours for conventional cTn assays.*8–12
1
*Adapted from the “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR
Guideline for the Evaluation and Diagnosis of Chest Pain.”13
Synopsis
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Chest pain is the second most common presenting complaint to EDs in the United States and has a wide array
of potential causes, including ACS.14 Although most patients with chest pain will not have an ultimate diagnosis
of ACS, a missed ACS event has significant implications
for the patient’s morbidity and mortality. Patients presenting with signs or symptoms of ACS should undergo
a history and physical examination, have timely electrocardiographic acquisition and interpretation (Table 3),
and assessment of cardiac troponin, because these tests
are central to the diagnosis of MI15 and will guide patient
management (Figure 3). A thorough description of the
evaluation of patients with suspected ACS is provided
in the “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/
SCMR Guideline for the Evaluation and Diagnosis of
Chest Pain.”13 Initial medical treatment should begin immediately for patients with presumed ACS. Urgent echocardiography, which may include an initial point-of-care
ultrasound by trained clinicians, is indicated for patients
with cardiogenic shock, hemodynamic instability, or for
suspected mechanical complications. For patients with
suspected STEMI, rapid reperfusion is critical after diagnosis, and further diagnostic testing should not delay cardiac catheterization or fibrinolytic therapy unless
it would immediately change patient management. For
patients who warrant additional testing to confirm a diagnosis of ACS, selection of the method of assessment
may encompass several factors, including clinical history,
electrocardiographic findings, cardiac biomarkers, patient preference, and patient exercise capacity. The use
of evidence-based clinical decision pathways (CDPs)
has been shown to improve outcomes and direct appropriate use of resources.13 CDPs reduce unnecessary
testing in 21% to 43% of patients while maintaining a
high negative predictive value for major adverse cardiovascular events (MACE).16–19
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Recommendation-specific Supportive Text
1. A focused history and rapid evaluation are critical in the assessment of a patient with suspected
ACS.13 Early recognition and initiation of therapy
for ACS improves outcomes.2,20 Rapid electrocardiographic acquisition and interpretation is required
for identification of STEMI (Table 3). In patients with
NSTE-ACS, the ECG may be normal or demonstrate
transient ST-segment elevation (a high-risk finding),
ST-segment depression, T-wave inversions, or nonspecific changes. Of note, ST-segment depression
in the anteroseptal leads (V1-V3) could indicate
an evolving posterior STEMI and therefore should
be managed with a high index of suspicion with a
posterior lead ECG if warranted (Table 3).21 Overall,
timely acquisition of an ECG is imperative in patients
with a goal to obtain and interpret an ECG by a
trained clinician within 10 minutes of presentation.1
2. An initial nondiagnostic 12-lead ECG does not “rule
out” or exclude ACS. Electrocardiographic abnormalities may be dynamic. A nondiagnostic ECG should be
compared to prior ECGs, and a repeat ECG should be
obtained during the ED course to assess for evolving
changes.3 Right-sided leads should be obtained in
patients with a concern for inferior STEMI to evaluate
for right ventricular involvement.22 Assessment for
posterior STEMI with an ECG is described in Table
3. The timing of repeat ECGs should be guided by
the patient’s symptoms, especially recurrent chest
pain, and any change in clinical condition.15 In NCDR
ACTION (National Cardiovascular Data Registry
and Acute Coronary Treatment and Intervention
Outcomes Network), 11% of patients ultimately
diagnosed with STEMI had an initial ECG that was
nondiagnostic, and 72.4% of those patients had a
follow-up ECG diagnostic of STEMI within 90 minutes of their initial ECG.3
3. cTn is the biomarker of choice for assessing patients
for possible cardiac injury, with hs-cTn assays being
preferred. cTn is central to the diagnosis of AMI.15
Given its high sensitivity and specificity for myocardial injury, cTn (I or T) should be utilized to detect
or exclude myocardial injury.7 In the setting of electrocardiographic evidence of STEMI, reperfusion
therapy should not be delayed pending biomarker
results. A cTn concentration >99th percentile upper
reference limit (a value unique to each assay) is an
indicator of myocardial injury.15,23,24 hs-cTn assays
are preferred over conventional cTn assays because
the sensitivity and negative predictive values of hscTn are greater.4,15 In addition, the time interval from
chest pain onset to detection of hs-cTn is shorter with
hs-cTn compared with conventional cTn assays, leading to more rapid “rule in” or “rule out” of ischemia.25
4. AMI is characterized by a rising and/or falling pattern
of cTn values with at least 1 value above the 99th
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Recommendations for Initial In-Hospital Assessment of Patients With
Confirmed or Suspected ACS (Continued )
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AND GUIDELINES
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Figure 3. Initial Assessment of Patients With Suspected ACS.
Colors correspond to Class of Recommendation in Table 2. *Examples of evidence-based CDPs and definition of low, intermediate, and high risk as
defined in the 2021 AHA/ACC/Multisociety Chest Pain Guideline. ACS indicates acute coronary syndromes; CDP, clinical decision pathway; cTn,
cardiac troponin; hs-cTn, high-sensitivity cardiac troponin; NSTEMI, non–ST-segment elevation myocardial infarction; and STEMI, ST-segment
elevation myocardial infarction. Adapted with permission from Gulati et al.13 Copyright 2021 American Heart Association, Inc., and American
College of Cardiology Foundation.
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2025 Acute Coronary Syndromes Guideline
3.1.3. Risk Stratification Tools for Patients With
STEMI and NSTE-ACS
Synopsis
Substantial variability in short-term mortality and MACE
risk exists among patients with ACS. Individual risk
assessment can inform discussions with patients and
decisions regarding therapeutic interventions. Several
risk scores have been developed and validated to help
assess a patient’s short- and long-term risk in established ACS using commonly available clinical and laboratory variables. Although several risk scores exist,1–3 the
GRACE (Global Registry of Acute Coronary Events) and
TIMI (Thrombolysis in Myocardial Infarction) Risk Scores
for NSTE-ACS and STEMI (Table 5) are well validated
and may be useful for helping to guide some therapeutic
decisions (Section 6.1., “Rationale and Timing for a Routine Invasive or Selective Invasive Approach”).4–7 These
scores are not to be used as diagnostic tools, because
they stratify patient risk in the setting of suspected or
confirmed ACS. Risk assessment using the GRACE Risk
Score has been found to be superior to subjective physician assessment for the prediction of death or MI in
patients with STEMI or intermediate-risk NSTE-ACS.8
However, there is insufficient evidence that routine
use of risk scores in patients hospitalized for STEMI/
NSTE-ACS translates into reduced risk of cardiovascular
events.9,10
Evidence of HF, such as pulmonary congestion
detected by physical examination, chest x-ray, or lung
ultrasound, is an important risk marker and integral part
of the Killip classification (and thereby the GRACE Risk
Score and TIMI Risk Score for STEMI) in patients with
ACS.11–15 Similarly, elevated cardiac biomarkers provide
prognostic information and also are key elements of
the GRACE and TIMI Risk Scores. Higher cTn levels in
patients with ACS are associated with an increased risk
of death and MACE16,17 and similarly may be useful for
helping to guide some treatment decisions.4,18 Several
other serum or plasma biomarkers may provide additional
prognostic information. In particular, natriuretic peptides
(including B-type natriuretic peptide and N-terminal pro-
Table 5. Selected Risk Stratification Tools for Patients With ACS
GRACE Risk Score (2.0)6,7
TIMI Risk Score for Unstable
Angina/NSTEMI*4
TIMI Risk Score for STEMI5
Target population
ACS
Unstable angina or NSTEMI
STEMI
Target outcome(s)
In-hospital, 6-mo, 1-y, 3-y, death or
death/MI
14-d all-cause death, MI, or urgent
revascularization
30-d all-cause death
Variables used
In-hospital risk score
Age ≥65 y
Age (65-74 y/≥75 y) (2-3 points)
Age
≥3 risk factors for CAD
Killip class II-IV (2 points)*
Killip class
Known coronary stenosis (≥50%)
Systolic blood pressure (<100 mm Hg, 3 points)
Systolic blood pressure
ST-segment deviation ≥0.5 mm
Heart rate >100 bpm (2 points)
Heart rate
≥2 anginal events in prior 24 h
Anterior ST-segment elevation or LBBB (1 point)
ST-segment deviation
Aspirin use in prior 7 d
Diabetes/hypertension/angina (1 point)
Cardiac arrest on admission
Elevated cardiac biomarkers (CK-MB or
troponin)
Weight (<67 kg, 1 point)
Serum creatinine
Time to treatment >4 h (1 point)
Elevated cardiac biomarkers
*Score 1 point for each characteristic that is present.
ACS indicates acute coronary syndromes; bpm, beats per minute; CAD, coronary artery disease; CK-MB, creatine kinase-myocardial band; GRACE, Global Registry
of Acute Coronary Events; LBBB, left bundle branch block; MI, myocardial infarction; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment
elevation myocardial infarction; and TIMI, Thrombolysis in Myocardial Infarction.
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percentile upper reference limit and believed caused
by myocardial ischemia.21 With the development of
hs-cTn assays enabling detection of circulating cTn
at lower concentrations, CDPs using serial testing of
hs-cTn at presentation (0 hours) and 1 to 2 hours later
provide high negative predictive value, as well as accelerated recognition of myocardial injury.9,1012 Clinicians
should be familiar with both the evidence-based CDPs
and the analytical characteristics of the cTn assay (ie,
limit of quantification, 99th percentile upper reference
limit, and criteria for significant change) used in their
practice.24,26 Men and women may have different cutoff values with hs-cTn assays. With hs-cTn assays,
changes in hs-cTn concentration within the normal
reference range but below the 99th percentile upper
reference limit can signal cardiac ischemia and may
warrant further evaluation. CDPs incorporating hscTn assays with repeat sampling at 1 or 2 hours from
ED arrival with calculation of the change or “delta”
hs-cTn can identify patients at very low risk (eg, negative predictive value >99.5%) based on assay-specific
diagnostic thresholds.8,11,27–30 However, when using
conventional cTn assays, the sampling timeframe is
extended to 3 to 6 hours from ED arrival.31 cTn may be
within normal range early after symptom onset especially when a high-sensitivity assay is not used. When
using a CDP that incorporates a single hs-cTn value,
the troponin should be obtained at least 3 hours after
the onset of symptoms.32
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AND GUIDELINES
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2025 Acute Coronary Syndromes Guideline
B-type natriuretic peptide) may identify those patients
with ACS at increased risk of death, HF, and recurrent
MACE.19,20
Early recognition of cardiogenic shock in patients
presenting with ACS on FMC by EMS or ED providers
is the key to initial triage and risk stratification.21 Cardiogenic shock related to AMI is present in 7% to 10% of
the ACS population and carries a high mortality rate.22
Early and rapid revascularization for cardiogenic shock
related to AMI is associated with increased survival, and
triage to a PCI-capable hospital and ideally to hospitals
providing advanced therapies (eg, mechanical circulatory
support [MCS]) is preferred (Section 8.1, “Revascularization in ACS With Cardiogenic Shock” and Section 8.2,
“MCS in Patients With ACS and Cardiogenic Shock”).
Several scales are available to determine the severity
of shock, and observational data have shown associations between severity as assessed by these scales and
outcomes.23
3.2. Management of Patients Presenting With
Cardiac Arrest
Recommendations for Management of Patients Presenting With
Cardiac Arrest
Referenced studies that support recommendations are summarized
in the Evidence Table.
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COR
LOE
Recommendations
1
C-LD
1. Patients with cardiac arrest and STEMI who have
been resuscitated should preferentially be
transferred by EMS to a PPCI-capable center.1,2
B-NR
2. Patients who have been resuscitated after cardiac
arrest and are noncomatose or who are comatose
with favorable prognostic features and with
evidence of STEMI, should undergo PPCI to
improve survival.3–7
C-LD
3. In patients with cardiac arrest who are comatose,
have unfavorable prognostic features, and evidence of STEMI, PPCI may be reasonable after
individualized assessment.4,7
A
4. In resuscitated patients who are comatose after
cardiac arrest, electrically and hemodynamically
stable, and without evidence of STEMI, immediate
angiography is not recommended due to lack of
benefit.8–14
1
2b
3: No
Benefit
Synopsis
Approximately 10% of patients with STEMI transferred
by EMS to the hospital are estimated to have an outof-hospital cardiac arrest.15 Early recognition of STEMI
in resuscitated patients and direct transfer to a PCIcapable center is associated with improved survival.1,2
Survival-to-hospital discharge in the patient who is comatose with out-of-hospital cardiac arrest is <10% regardless of etiology.16 Those with a witnessed arrest and
a shockable rhythm have improved survival. Outcomes
for patients with STEMI who are awake after resuscitated cardiac arrest are comparable to patients with STEMI
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who were not in cardiac arrest.3 For this reason, patients
with cardiac arrest who have achieved return of spontaneous circulation (ROSC) and are awake with STEMI on
ECG are candidates for PPCI. However, care should be
individualized in the comatose patient with rapid assessment of the patient’s clinical features and cardiac arrest
characteristics before proceeding with invasive angiography.17–19 In contrast, patients who are stable without
ST-segment elevation after out-of-hospital cardiac arrest
do not require immediate coronary angiography. Coronary angiography can be deferred pending further risk
stratification.8–13
Recommendation-Specific Supportive Text
1. Observational studies have shown an association
between triage of out-of-hospital cardiac arrest
patients to a PCI-capable facility with improved
outcomes.1,2,15 Data from the CARES (Cardiac
Arrest Registry to Enhance Survival) registry
showed that transfer to a PCI-capable center was
associated with improved survival in patients with
cardiac arrest and STEMI on ECG. EMS should
preferentially transfer patients who are comatose
after cardiac arrest, have achieved ROSC, and have
STEMI on the ECG to a PPCI center.2 Although
the ARREST (Advanced Reperfusion Strategies
for Patients With Out of Hospital Cardiac Arrest
and Refractory Ventricular Fibrillation) trial did not
show a benefit in triaging patients to primary cardiac arrest centers, this study evaluated patients
without STEMI on the ECG.20
2. Nearly one-third of patients with cardiac arrest and
STEMI on ECG have normal neurologic status on
presentation to the ED.3 Being alert or with partial/
minimal neurologic response on presentation with
STEMI after cardiac arrest is an independent predictor of survival. Observational studies have demonstrated comparable survival of the awake patient
with STEMI with cardiac arrest to those patients
with STEMI without cardiac arrest.3 For this reason,
patients with STEMI who have achieved ROSC and
are awake should undergo PPCI (Section 5.2.1,
“PPCI in STEMI”).
3. In patients who are comatose after cardiac arrest
and have achieved ROSC, but have STEMI on the
ECG, an individualized patient assessment for survival and futility is essential before proceeding with
PCI. Observational data have identified poor prognostic features that have been validated and incorporated into risk scores for this population. These
include unwitnessed arrest, no bystander cardiopulmonary resuscitation, nonshockable rhythm,
cardiopulmonary resuscitation >30 minutes, time
to ROSC >30 minutes, arterial pH <7.2, lactate
>7 mmol/L, age >85 years, and end-stage renal
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2025 Acute Coronary Syndromes Guideline
4. STANDARD MEDICAL THERAPIES FOR
STEMI AND NSTE-ACS
4.1. Oxygen Therapy
Recommendations for Oxygen Therapy
Referenced studies that support recommendations are summarized
in the Evidence Table.
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COR
LOE
Recommendations
1
C-LD
1. In patients with ACS and confirmed hypoxia
(oxygen saturation <90%), supplemental
oxygen to increase oxygen saturations to
≥90% is recommended to improve myocardial
oxygen supply and decrease anginal
symptoms.1
3: No
Benefit
A
2. In patients with ACS and oxygen saturations
≥90%, routine administration of supplemental
oxygen is not recommended because it does
not improve cardiovascular outcomes.2–4
Synopsis
Supplemental oxygen has historically been administered
as part of routine care in the management of patients
with suspected ACS, although evidence to suggest clinical benefit in the absence of hypoxia has been lacking.5
Randomized trials that have enrolled patients with MI
and without hypoxia have not demonstrated any clinical benefit from routine use of supplemental oxygen
(≥6 L/min)2–4,6 and have raised some concerns that it
may increase myocardial injury by increasing vasoconstriction and increasing oxidative stress.3
Recommendation-Specific Supportive Text
1. Use of supplemental oxygen may provide benefit to
patients who present with hypoxia (peripheral capillary oxygen saturations <90%), including those who
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
present with acute or chronic conditions that require
the need for supplemental oxygen to achieve an
oxygen saturation ≥90%. A systematic review and
meta-analysis of RCTs in acutely ill adults from
various causes without hypoxia suggested worse
short- and long-term mortality with liberal compared
with conservative administration of supplemental
oxygen.7 These studies were unable to define the
optimal oxygen saturation target range to minimize
potential harm and maximize clinical benefit. The
observed relationship between oxygenation and
outcomes appears to be U-shaped with the lowest
mortality rate described for those patients with an
Spo2 of 94% to 96% at presentation.8
2. Several randomized trials have now demonstrated
a lack of cardiovascular benefit with routine use of
supplemental oxygen in patients presenting with
known or suspected AMI and oxygen saturations
≥90%. Although exclusion criteria varied among
studies, patients with a home oxygen requirement,
active bronchospasm requiring supplemental oxygen, or with cardiac arrest at presentation were
excluded.2–4,6 The AVOID (Air Versus Oxygen in
ST-Segment-Elevation Myocardial Infarction) trial
investigated the effects of supplemental oxygen
(8 L/min) in patients with STEMI and oxygen saturations ≥94% and demonstrated a lack of benefit
with routine supplemental oxygen, including a possible increase in myocardial injury and infarct size.3
DETO2X-AMI (Efficacy and Outcome Study of
Supplemental Oxygen Treatment in Patients With
Suspected Myocardial Infarction) evaluated the use
of routine supplemental oxygen (6 L/min) in 6629
patients with suspected MI and an oxygen saturation ≥90%.2 The use of supplemental oxygen did
not reduce all-cause mortality at 1 year and did not
reduce rehospitalization with MI.2,9 A consistent lack
of clinical benefit was seen in the study for those with
lower baseline oxygen saturations (90%-94%).10
4.2. Analgesics
Synopsis
Patients presenting with known or suspected ACS often
experience chest pain or other uncomfortable symptoms.
Rapid and effective pain relief remains an important treatment goal to prevent sympathetic activation and adverse
clinical sequelae (Table 6). Analgesic therapies may provide symptomatic relief, but they have not been shown
to improve clinical outcomes in patients with ACS.1,2 Nitrates and opiate medications remain effective treatment
options for management of pain in ACS but should be
thoughtfully utilized to prevent potential harm.3–6 In particular, rapid coronary revascularization should be pursued for patients with ongoing ischemic symptoms that
are not relieved with nitrates, and opiates should not be
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AND GUIDELINES
disease on dialysis.4,21–30 Although these data suggest a lack of clear benefit for invasive therapies
for patients with STEMI and cardiac arrest who
have features indicating an unfavorable neurologic prognosis,4,7 this has not been validated in
prospective trials. However, for those patients with
favorable prognostic features, PPCI is associated
with greater survival.4,7,27
4. Six contemporary trials9–14 have evaluated the
role of emergency angiography in patients who
remain comatose after cardiac arrest, do not have
ST-segment elevation on a 12-lead ECG, and are
electrically and hemodynamically stable. These
studies consistently demonstrated a lack of benefit
to early angiography when compared with delayed
or no angiography in the study population with comparable in-hospital and 6-month survival, as well as
neurologic recovery.31 The relative utility of delayed
coronary angiography in this population is uncertain.
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2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
Table 6. Analgesic Treatment Options for Cardiac Chest Pain
Medication
Route
Suggested Dosing
Considerations
Nitroglycerin*
SL (tablets, spray)
0.3 or 0.4 mg every 5 min as needed
up to a total of 3 doses
Use in hemodynamically stable patients with SBP ≥90 mm Hg.
Nitroglycerin*
IV
Start at 10 μg/min and titrate to pain
relief and hemodynamic tolerability.
Consider for persistent anginal pain after oral nitrate therapy, or if ACS is
accompanied by hypertension or pulmonary edema.20–22 Avoid use in suspected
RV infarction, SBP <90 mm Hg or a change in SBP >30 mm Hg below baseline.
Tachyphylaxis may occur after approximately 24 h.
Morphine
IV
2-4 mg; may repeat if needed every
5-15 min. Doses up to 10 mg may be
considered.
Use for relief of pain that is resistant to other maximally tolerated anti-ischemic
medications. May delay the effects of oral P2Y12 therapy.7,9–12 Monitor closely for
adverse effects.
Fentanyl
IV
25-50 μg; may repeat if needed.
Doses up to 100 μg may be considered.
Use for relief of pain that is resistant to other maximally tolerated anti-ischemic
medications. May delay the effects of oral P2Y12 therapy.8 Monitor closely for
adverse effects.
*Nitrates should not be administered after recent PDE5 inhibitor use. Avoid use of nitrates/nitroglycerin within 12 h of avanafil, 24 h of sildenafil/vardenafil, or 48 h
of tadalafil.23–25
ACS indicates acute coronary syndromes; PDE5, phosphodiesterase-5 inhibitor; RV, right ventricular; SBP, systolic blood pressure; and SL, sublingual.
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used solely to mask these symptoms. Concerns have also
been raised that the use of opiates may delay gastric
and intestinal absorption of orally administered P2Y12
inhibitors, thereby delaying their pharmacodynamic effects in patients undergoing PCI.7–10 However, the clinical
relevance of these pharmacodynamic findings remains
disputed.11–14 Use of nonaspirin nonsteroidal anti-inflammatory drugs should be avoided for management of suspected or known ischemia pain whenever possible.15–17
Use of nonsteroidal anti-inflammatory drugs is associated
with increased risk of MACE in patients with and without
prior cardiac disease, with no documented benefit to support routine use in patients with ACS.15–19
4.3. Antiplatelet Therapy
4.3.1. Aspirin
Recommendation for Aspirin
Referenced studies that support recommendations are summarized
in the Evidence Table.
COR
LOE
Recommendation
1
A
1. In patients with ACS, an initial oral loading
dose of aspirin, followed by daily low-dose
aspirin, is recommended to reduce death
and MACE.1–5
Synopsis
Aspirin has long been considered an integral part of antiplatelet therapy to prevent recurrent atherothrombotic
events among patients with ACS.1–3,6 Aspirin reduces the
incidence of vascular death after AMI,3 and in secondary prevention trials (that include patients after MI), it reduces the occurrence of vascular and coronary events,
including MI and stroke.2 Although aspirin use after ACS
was traditionally considered lifelong, a strategy of aspirin
discontinuation, rather than P2Y12 inhibitor discontinuation, may now be considered in the maintenance phase
after 1 to 3 months in selected patients to reduce risk of
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bleeding (Section 11.1, “DAPT Strategies in the First 12
Months Postdischarge”). Aspirin discontinuation after 1
to 4 weeks after PCI is also appropriate for patients on
a full-dose anticoagulant in combination with continued
use of a P2Y12 inhibitor (Section 11.1.1, “Antiplatelet
Therapy in Patients on Anticoagulation Postdischarge”).
For patients in whom a history of aspirin hypersensitivity
is reported, aspirin desensitization is preferred whenever
possible to allow for initial use of dual antiplatelet therapy.7–9 The use of a P2Y12 inhibitor is recommended in
all patients with ACS regardless of whether they have a
history of aspirin hypersensitivity, but should be administered with a loading dose as early as possible for those
patients unable to take aspirin at presentation.
Recommendation-Specific Supportive Text
1. Aspirin should be initiated with a loading dose
(162-325 mg) in patients with ACS without an
absolute contraindication as soon as possible on
presentation irrespective of final management
strategy (invasive or noninvasive), followed by a
daily maintenance dose (Table 7 in Section 4.3.2,
“Oral P2Y12 Inhibitors During Hospitalization”). In
patients who cannot take oral medication, rectal or
intravenous (where available) administration are
options for administration. Current evidence supports the use of uncoated low-dose aspirin (75100 mg) for daily maintenance therapy. The 75 to
100 mg daily dose of aspirin exceeds the minimal
effective dose required for platelet thromboxane A2
suppression, allowing for some interindividual variability in drug response.10 Among patients with ACS
referred for an invasive strategy, continued use of
full-dose aspirin (300-325 mg daily) for 30 days
(following an initial loading dose) was not superior
to low-dose aspirin (75-100 mg daily) for reduction
of MACE but was associated with increased minor
and gastrointestinal bleeding.4 In an open-label
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2025 Acute Coronary Syndromes Guideline
Table 7. Dosing Considerations for Oral Antiplatelet Therapy in Patients With ACS
Setting
Dosing Considerations
Aspirin
NSTE-ACS or STEMI
Loading dose 162-325 mg orally. Aspirin (nonenteric coated) should be chewed, when
possible, to achieve faster onset of antiplatelet action. Loading dose should be
administered for patients already on aspirin therapy.
CLINICAL STATEMENTS
AND GUIDELINES
Agent
Maintenance dose 75-100 mg orally daily (nonenteric coated)
Clopidogrel
NSTE-ACS or STEMI without fibrinolytic
Loading dose 300 or 600 mg orally
Maintenance 75 mg orally daily
STEMI with fibrinolytic
Loading dose 300 mg orally if age ≤75 y; Initial dose 75 mg orally if age >75 y
Maintenance 75 mg orally daily
Prasugrel
NSTE-ACS or STEMI without fibrinolytic, and
undergoing PCI
Loading dose 60 mg orally
Maintenance dose 10 mg orally daily if body weight ≥60 kg and age <75 y
Maintenance dose 5 mg orally daily if body weight <60 kg or age ≥75 y (use caution)
Ticagrelor
NSTE-ACS or STEMI without fibrinolytic
Loading dose 180 mg orally
Maintenance dose 90 mg orally twice daily
NSTE-ACS indicates non–ST-segment elevation acute coronary syndromes; PCI, percutaneous coronary intervention; and STEMI, ST-segment elevation myocardial
infarction.
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RCT of patients with established atherosclerotic
cardiovascular disease (ASCVD), 35% of whom
had a previous MI, no significant differences were
observed in MACE or major bleeding for patients
treated with 81 mg of aspirin daily and those
treated with 325 mg daily, although a high degree
of crossover between study arms was observed.5
Together, these data support the use of low-dose
aspirin (75-100 mg daily) for maintenance therapy.
Based on an association between aspirin dosing
and outcomes in a post hoc analysis of the PLATO
(Platelet Inhibition and Patient Outcomes) trial,
aspirin doses of ≤100 mg daily should always be
used in patients treated with ticagrelor.11
Recommendations for Oral P2Y12 Inhibitors During Hospitalization
(Continued )
COR
2b
LOE
Recommendations
B-NR
6. In patients with NSTE-ACS planned for an invasive strategy with timing of angiography anticipated to be >24 hours, upstream treatment with
clopidogrel or ticagrelor may be considered to
reduce MACE.1,5,8
In-Hospital Management in Patients With STEMI
B-R
7. In patients with STEMI managed with PPCI,
prasugrel or ticagrelor should be administered to
reduce MACE and stent thrombosis.4,5,9,10
1
C-LD
8. In patients with STEMI managed with PPCI,
clopidogrel is recommended to reduce MACE and
stent thrombosis when prasugrel or ticagrelor
are unavailable, cannot be tolerated, or are
contraindicated.11
1
A
9. In patients with STEMI managed with fibrinolytic
therapy, clopidogrel should be administered
concurrently to reduce death and MACE.2,3
1
4.3.2. Oral P2Y12 Inhibitors During Hospitalization
Recommendations for Oral P2Y12 Inhibitors During Hospitalization
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
LOE
Recommendations
All Patients With ACS (STEMI and NSTE-ACS)
1
3: Harm
A
1. In patients with ACS, an oral P2Y12 inhibitor
should be administered in addition to aspirin to
reduce MACE.1–5
B-R
2. In patients with a history of stroke or transient
ischemic attack, prasugrel should not be administered because of worse net clinical outcomes.*†4
In-Hospital Management in Patients With NSTE-ACS
1
B-R
3. In patients with NSTE-ACS undergoing PCI,
prasugrel or ticagrelor is recommended to reduce
MACE and stent thrombosis.4–6
1
B-R
4. In patients with NSTE-ACS who are managed
without planned invasive evaluation, ticagrelor is
recommended to reduce MACE.5,7
B-R
5. In patients with NSTE-ACS, clopidogrel is
recommended to reduce MACE when prasugrel
or ticagrelor are unavailable, cannot be tolerated,
or are contraindicated.1
1
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization”12 and the
†”2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management
of Patients With Chronic Coronary Disease.”13
Synopsis
Oral inhibitors of the platelet P2Y12 receptor antagonize adenosine diphosphate–mediated activation of
platelets. Across the spectrum of ACS, the addition of a
P2Y12 inhibitor to aspirin significantly reduces platelet
aggregation and has been shown to reduce the incidence of recurrent MACE but with an increased risk of
bleeding.1–5,9,10 In addition to receiving aspirin, patients
with ACS should therefore be treated with a loading
dose of an oral P2Y12 inhibitor followed by daily dosing (Table 7). The selection of the specific type of oral
P2Y12 inhibitor should involve several considerations,
including the patient’s anticipated management strat-
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egy and their risk of bleeding (Figure 4).1–5,9,10 Clinically
available oral P2Y12 inhibitors include clopidogrel, prasugrel, and ticagrelor. Clopidogrel is the least potent
oral P2Y12 inhibitor and requires more time to reach
its maximal platelet inhibition after a loading dose, because it requires biotransformation in the liver to form
its active metabolite. Pharmacodynamic variability in
response in clopidogrel has been well described,14,15
and hyporesponders may be at increased risk of MACE
and stent thrombosis when treated with clopidogrel after PCI.16,17 Ticagrelor and prasugrel are more potent
than clopidogrel and achieve more rapid onset of inhibition of platelet activation but with increased risk of
bleeding compared with clopidogrel. Of note, ticagrelor
may cause subjective transient dyspnea in approximately 10% to 15% of patients after ACS.5 The topic
of duration of dual antiplatelet therapy is addressed in
Section 11.1, “DAPT Strategies in the First 12 Months
Postdischarge.”
Recommendation-Specific Supportive Text
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1. Several trials have demonstrated the clinical benefit of oral P2Y12 inhibitors in ACS for reducing
MACE but with increased risk of bleeding. In randomized placebo-controlled trials in both NSTEACS and STEMI, the addition of clopidogrel to
aspirin reduced risk of MACE irrespective of management strategy.1–3 In patients with STEMI treated
with fibrinolytic therapy, the addition of clopidogrel to aspirin reduces 30-day MACE, including
2025 Acute Coronary Syndromes Guideline
recurrent MI, and improves survival.2,3 Moreover, in
randomized trials, the use of prasugrel and ticagrelor further reduced risk of MACE, as well as stent
thrombosis, when compared with clopidogrel in
patients with STEMI (not receiving concurrent
fibrinolytic therapy) or NSTE-ACS.4,5 The benefits
of oral P2Y12 inhibitors have also been demonstrated in patients after coronary artery bypass
graft (CABG) surgery.18–21 Guidance on dosing
interruption for patients referred for CABG is in
Table 8. Duration of administration after CABG is
described in Section 11.1, “DAPT Strategies in the
First 12 Months Postdischarge.”
2. In a secondary analysis of the randomized,
double-blind TRITON-TIMI 38 (Trial to Assess
Improvement in Therapeutic Outcomes by
Optimizing Platelet Inhibition with Prasugrel–
Thrombolysis in Myocardial Infarction) of prasugrel
versus clopidogrel in addition to aspirin among
patients with ACS, subgroup analyses using an
outcome of net clinical benefit (MACE events plus
bleeding) demonstrated net harm with prasugrel
versus clopidogrel among patients with previous
transient ischemic attack or stroke.4 Dose reduction of prasugrel should be considered in patients
≥75 years of age and in those with a body weight
<60 kg (Table 7).
3. The randomized, double-blind TRITON-TIMI 38
and PLATO trials demonstrated that prasugrel (TRITON-TIMI 38) or ticagrelor (PLATO)
reduced the rate of the composite endpoint of
Figure 4. Initial Choice of P2Y12 Inhibitor in Patients Not Requiring an Oral Anticoagulant.
Colors correspond to Class of Recommendation in Table 2.
ACS indicates acute coronary syndromes; ASA, aspirin; CABG, coronary artery bypass grafting; NSTE-ACS, non–ST-segment elevation ACS; PCI,
percutaneous coronary intervention; and STEMI, ST-segment elevation myocardial infarction.
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Clopidogrel
Elective CABG: Interrupt for 5 d before surgery.
Urgent CABG: Interruption for at least 24 h (ideally) and
proceeding earlier than 5 d may be reasonable.
Prasugrel
Elective CABG: Interrupt for 7 d before surgery.
Urgent CABG: Interruption for at least 24 h (ideally) and
proceeding earlier than 7 d may be reasonable.
Ticagrelor
Elective CABG: Interrupt for 3-5 d before surgery.
Urgent CABG: Interruption for at least 24 h (ideally) and
proceeding earlier than 5 d may be reasonable.
*For all patients, oral P2Y12 inhibitor should be resumed after surgery when
bleeding risk not excessive (typically 24-72 hours).
CABG indicates coronary artery bypass grafting.
Downloaded from http://ahajournals.org by on February 28, 2025
cardiovascular death, MI, or stroke by 16% to
20% when compared with clopidogrel, as well
as reduced the risk of stent thrombosis.4,5 In the
PLATO trial, a nominal reduction in all-cause
death with ticagrelor compared with clopidogrel was also observed.5 In TRITON-TIMI 38, the
P2Y12 inhibitor (prasugrel or clopidogrel) was
only administered in patients with NSTE-ACS
once the anatomy was deemed suitable for PCI.
In the PLATO trial, 72% were managed with a
planned invasive strategy and results in the invasively managed population were highly consistent
with the overall trial for reducing MACE, as well as
cardiovascular and all-cause death individually.6
Both prasugrel and ticagrelor increase the risk of
non-CABG major bleeding compared with clopidogrel.4,5 Prasugrel has been shown to increase
life-threatening bleeds.4 Limited data exist to
compare the efficacy and safety of prasugrel versus ticagrelor head-to-head. One open-label randomized trial reported a lower rate of MACE with
similar bleeding with prasugrel administered at
the time of PCI compared with ticagrelor used as
upstream therapy in patients with ACS undergoing invasive evaluation.22
4. The randomized, double-blind PLATO trial of
ticagrelor versus clopidogrel included patients
with ACS managed with or without a planned
invasive strategy. Among the 28% of patients
(n=5216) who were managed without a planned
invasive strategy, a 15% reduction was observed
in the primary endpoint of vascular death, MI,
or stroke with ticagrelor versus clopidogrel that
was highly consistent with the 16% reduction in
MACE in the overall trial. Similarly, the findings
for bleeding were consistent with the overall trial
result.5,7
5. In the randomized, double-blind, placebo-controlled CURE (Clopidogrel in Unstable Angina to
Prevent Recurrent Events) trial, among patients
with NSTE-ACS receiving aspirin and who were
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
medically managed or underwent revascularization, the administration of clopidogrel significantly
reduced the composite of cardiovascular death,
MI, or stroke.1 Although prasugrel and ticagrelor further reduce major cardiovascular events
compared with clopidogrel in patients with ACS
undergoing PCI, these more potent agents
also further increase the risk of bleeding.4,5
Clopidogrel is an effective alternative P2Y12
inhibitor for use in patients with high bleeding
risk or contraindications to prasugrel or ticagrelor.
In an open-label trial with a high crossover rate
among older patients with ACS undergoing PCI,
patients treated with clopidogrel had a similar rate
of ischemic events and less bleeding compared
with ticagrelor.23 Significant interpatient variability
in the pharmacodynamic response to clopidogrel
has been described.15
6. In a prospective substudy among the patients
who underwent PCI (n=2658) in the CURE
trial, those who were pretreated with clopidogrel
(median 6 days) prior to PCI had a significantly
lower rate of MACE both before PCI and by 30
days.8 Clopidogrel is a prodrug that requires
metabolism by the cytochrome P450 enzyme
system to form its active metabolite and therefore may require several hours before significant
antiplatelet effect is observed following a loading dose. A meta-analysis of trials of clopidogrel in patients with ACS undergoing PCI found
that pretreatment with clopidogrel significantly
reduced the risk for 30-day cardiovascular death
or MI.11 However, less is known regarding the
need for pretreatment in the era of more potent
P2Y12 inhibitors with more rapid onset of antiplatelet action. In a randomized trial of prasugrel
pretreatment versus administration at the time of
PCI, pretreatment (median of only 4.4 hours) did
not improve ischemic outcomes, but significantly
increased bleeding.24 In the PLATO trial, knowledge of coronary anatomy prior to administration of the study drug was not required; however,
upstream use of ticagrelor was not specifically
compared with a strategy of administration at
time of PCI. Therefore, it remains unknown
whether a benefit exists for administration of
ticagrelor prior to PCI in patients with NSTEACS. For this reason, routine pretreatment in
patients undergoing an early invasive management strategy (<24 hours) is not supported by
clinical trial data. However, it may be reasonable to consider pretreatment with clopidogrel
or ticagrelor in patients undergoing an invasive
management strategy with the timing of angiography anticipated to be ≥24 hours from administration of the loading dose.
TBD TBD, 2025
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Table 8. Management of Oral P2Y12 Inhibitors for Patients
Who Require CABG Surgery*
CLINICAL STATEMENTS
AND GUIDELINES
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7. The clinical efficacy of prasugrel and ticagrelor compared with clopidogrel in TRITON-TIMI 38 and the
PLATO trial was consistent in patients undergoing PPCI or delayed (ie, secondary) PCI after initial
therapy for STEMI.4,5 In the subgroup of patients with
STEMI in TRITON-TIMI 38 (n=3534), prasugrel significantly reduced MACE by 21% and stent thrombosis by 42% at 15 months without a clear excess
in bleeding.9 In the PLATO trial, compared with clopidogrel, treatment of patients with STEMI undergoing
PPCI (n=7544) with ticagrelor was associated with
a consistent trend toward reduction in cardiovascular death, recurrent MI, or stroke, as well as a significant reduction in stent thrombosis and an 18%
reduction in all-cause death.10 Both TRITON-TIMI 38
and the PLATO trial permitted study drug administration prior to the initial angiogram for patients with
STEMI undergoing primary PCI. In a separate randomized trial in PPCI for STEMI, allocation to prehospital ticagrelor or hospital administration did not
improve the primary endpoint of coronary reperfusion prior to the PCI.25 However, upstream administration of ticagrelor was associated with a reduction
in stent thrombosis with similar bleeding between
treatment groups. Registry data have also not shown
clear clinical benefit for preloading a P2Y12 inhibitor in patients with STEMI,26 but a meta-analysis that
included patients with STEMI showed that clopidogrel pretreatment was associated with a lower risk
for MACE without an increase in bleeding.27
8. Clopidogrel is effective for prevention of stent
thrombosis and early recurrent ischemic events
in patients with STEMI undergoing PCI.11 As in
patients with NSTE-ACS, in patients with STEMI
undergoing PPCI, prasugrel and ticagrelor reduce
the risk of recurrent MACE compared with clopidogrel.9,10 Administration of clopidogrel is an alternative to prasugrel or ticagrelor in patients with
STEMI who are at high bleeding risk or have other
contraindications to those agents.
9. In the CLARITY (Clopidogrel as Adjunctive
Reperfusions Therapy)-TIMI 28 trial, addition of
clopidogrel to aspirin in patients with STEMI who
were <75 years of age and received fibrinolytic therapy reduced the odds of an occluded infarct-related
artery at angiography, as well as the composite of
cardiovascular death, recurrent MI, or recurrent
ischemia requiring urgent revascularization by
30 days.2 In the randomized, placebo-controlled
COMMIT (Clopidogrel and Metoprolol in Myocardial
Infarction Trial) study among patients with suspected
MI (93% STEMI, 54% fibrinolytic-treated) receiving
aspirin, clopidogrel 75 mg/day (without a loading
dose), significantly lowered the risk of the composite endpoint of death, reinfarction, or stroke, as well
as the endpoint of mortality alone, with a consistent
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2025 Acute Coronary Syndromes Guideline
pattern in the subgroup treated with fibrinolytic.3 No
significant excess was observed in bleeding with
clopidogrel versus placebo. Based on the design of
these 2 trials, when administered concurrently with
fibrinolytic as the reperfusion strategy, clopidogrel
is recommended to be administered with a loading
dose (300 mg, then 75 mg daily) for patients <75
years of age and starting without a loading dose (75
mg daily) for patients ≥75 years of age. In patients
treated with a fibrinolytic agent who are undergoing
subsequent PCI, either clopidogrel or ticagrelor (age
<75 years, within 24 hours after a fibrinolytic agent)
or prasugrel (>24 hours after a fibrinolytic agent) are
alternatives to support PCI.9–12,28 In a trial of 3799
patients with STEMI who were treated with a fibrinolytic agent, 89% of whom also received clopidogrel
at the time of a fibrinolytic agent, randomization to
ticagrelor administered at a median of 11.4 hours
(interquartile range, 5.8-18.2 hours) after fibrinolytic
therapy was noninferior to clopidogrel with respect
to major bleeding.28
4.3.3. Intravenous P2Y12 Inhibition
Recommendation for Intravenous P2Y12 Inhibition
Referenced studies that support recommendations are summarized
in the Evidence Table.
COR
LOE
Recommendation
2b
B-R
1. Among patients with ACS undergoing PCI who
have not received a P2Y12 inhibitor, intravenous
cangrelor may be reasonable to reduce
periprocedural ischemic events.*1–4
*Reproduced from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery
Revascularization.”5
Synopsis
Cangrelor is a direct-acting, intravenous antagonist of the
P2Y12 receptor characterized by rapid and potent platelet
inhibitory effects with restoration of platelet function occurring within 1 hour of drug discontinuation.6 These pharmacological properties may be particularly beneficial in clinical
scenarios wherein absorption of orally administered P2Y12
inhibitors is impaired or not possible, as well as in patients
requiring CABG or other surgery early after PCI when prolonged discontinuation of a P2Y12 inhibitor may not be
safe.7 The safety and efficacy of cangrelor has been compared with clopidogrel or placebo in 3 RCTs involving patients who are P2Y12 inhibitor-naïve and undergoing PCI
for stable or acute indications.1–3 In a patient-level pooled
analysis of these studies, cangrelor administered during PCI
significantly reduced periprocedural ischemic events albeit
at the expense of more frequent minor bleeding.4 The safety and efficacy of cangrelor versus ticagrelor or prasugrel
with respect to ischemic events have not been established.
The transition from intravenous to oral P2Y12 inhibition is
an important consideration to ensure adequate platelet inhibition on completion of cangrelor infusion (Table 9).8
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2025 Acute Coronary Syndromes Guideline
Recommendations for Intravenous Glycoprotein IIb/IIIa Inhibitors
(Continued )
Timing of Loading Dose Administration
COR
600 mg
Immediately after discontinuation
of cangrelor
3: Harm
Prasugrel
60 mg
Immediately after discontinuation
of cangrelor
Ticagrelor
180 mg
At any time during or immediately
after discontinuation of cangrelor
Oral P2Y12 inhibitor
Loading Dose
Clopidogrel
Recommendations in table obtained from US Food and Drug Administration
labeling for cangrelor.8
Recommendation-Specific Supporting Text
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1. CHAMPION PHOENIX (A Clinical Trial Comparing
Cangrelor to Clopidogrel Standard Therapy in Subjects
Who Require PCI) examined the effect of cangrelor versus clopidogrel in patients undergoing PCI for
acute or stable coronary syndromes.2 Cangrelor was
administered as an intravenous bolus prior to PCI followed by an infusion for at least 2 hours or for the
duration of the procedure, whichever was longer. In
the control arm, clopidogrel was administered as a
600- or 300-mg loading dose immediately before or
after PCI. At 48 hours, the primary endpoint of allcause death, MI, ischemia-driven revascularization,
or stent thrombosis was significantly reduced with
cangrelor with similar effects observed among those
presenting with NSTE-ACS (n=2810) or STEMI
(n=1991). These results contrast with the earlier
neutral findings from the CHAMPION PLATFORM
(Cangrelor Versus Standard Therapy to Achieve
Optimal Management of Platelet Inhibition) trial and
CHAMPION PCI (A Clinical Trial to Demonstrate
the Efficacy of Cangrelor), which compared cangrelor with placebo and clopidogrel, respectively.1,3
Differences across trials in the timing of clopidogrel
administration and definitions of MI and stent thrombosis may in part account for variability in the incidence of ischemic events and observed treatment
effect. In a pooled analysis of these trials, cangrelor
was associated with a significant reduction in periprocedural ischemic events compared with control
with no evidence of heterogeneity across types of
ACS presentations.4
4.3.4. Intravenous Glycoprotein IIb/IIIa Inhibitors
Recommendations for Intravenous Glycoprotein IIb/IIIa Inhibitors
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
2a
LOE
Recommendations
C-LD
1. In patients with ACS undergoing PCI with large
thrombus burden, no-reflow, or slow flow, adjunctive
use of an intravenous or intracoronary glycoprotein
IIb/IIIa inhibitor is reasonable to improve procedural
success and reduce infarct size.*,1,2
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LOE
Recommendations
B-R
2. In patients with ACS, glycoprotein IIb/IIIa
inhibitors should not be administered routinely
due to lack of ischemic benefit and increased risk
of bleeding.3–5
*Adapted from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery
Revascularization.”6
Synopsis
Glycoprotein IIb/IIIa receptor inhibitors are parenterally administered drugs that block platelet aggregation by preventing platelet cross-linking via fibrinogen
or von Willebrand factor binding to the glycoprotein
IIb/IIIa receptor. These agents were first evaluated before contemporary antiplatelet and interventional strategies were introduced and in an era when the time to
coronary revascularization was substantially longer than
today. Thus, limited data are available for glycoprotein
IIb/IIIa receptors in patients receiving more potent
P2Y12 inhibitors and in those receiving earlier PCI with
contemporary drug-eluting stents that have a lower risk
for stent thrombosis than prior generations of stents. In
current practice, the role of glycoprotein IIb/IIIa receptor inhibitors is largely limited to adjunctive use at the
time of PCI in patients with large thrombus burden or as
“rescue” or “bailout” therapy in patients with PCI complications such as no-reflow or persistent or recurring
thrombus at the lesion.1
Recommendation-Specific Supportive Text
1. In a study of 452 selected high-risk patients with
large anterior STEMI and a large thrombus burden, adjunctive use of intracoronary abciximab
reduced thrombus burden and infarct size.1 Other
trials have also suggested that glycoprotein IIb/IIIa
inhibitors can reduce intracoronary thrombus
burden in patients with STEMI and NSTE-ACS.7,8
Thus, glycoprotein IIb/IIIa receptor inhibitors can
be considered at the time of PCI for patients with
a large coronary thrombus burden or no-reflow
or slow flow that is believed to be attributable to
distal embolization of thrombus. In clinical trials
comparing intravenous and intracoronary administration of glycoprotein IIb/IIIa inhibitors, clinical and bleeding outcomes, as well as thrombus
resolution and infarct size, have generally been
similar.2,9,10
2. Multiple strategies have been evaluated for use of
glycoprotein IIb/IIIa receptor inhibitors in patients
with ACS. “Upstream” administration of these
agents is defined as administration of small molecule agents (eptifibatide or tirofiban) early after
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CLINICAL STATEMENTS
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Table 9. Transition From Intravenous Cangrelor Infusion to
Oral P2Y12 Inhibitor
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2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
ACS diagnosis for medical stabilization prior to
planned angiography and PCI. In the EARLY-ACS
(Early Glycoprotein IIb/IIIa Inhibition in Patients
with Non–ST-segment Elevation Acute Coronary
Syndrome) trial, 9406 patients with NSTE-ACS
were randomized to routine upstream use of eptifibatide (within 8 hours after presentation to the
hospital) versus ad hoc adjunctive use at the time
of PCI among patients with NSTE-ACS.4 Ischemic
outcomes were not improved and bleeding was
increased in the routine upstream eptifibatide arm.
An alternative approach is routine adjunctive use
of a glycoprotein IIb/IIIa inhibitor at the time of PCI
for patients with STEMI or NSTE-ACS. Although
early trials performed prior to use of potent P2Y12
inhibitors suggested that this approach improved
procedural outcomes and reduced periprocedural
myocardial necrosis, studies performed among
patients receiving pretreatment with clopidogrel
have not confirmed reduction of ischemic events
with routine adjunctive glycoprotein IIb/IIIa inhibition and have increased bleeding complications.5,11
4.4. Parenteral Anticoagulation
Recommendations for Parenteral Anticoagulation
Referenced studies that support recommendations are summarized
in the Evidence Table.
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COR
LOE
Recommendations
NSTE-ACS: Upstream* Anticoagulant Therapy
1
1
B-R
1. In patients with NSTE-ACS, intravenous
unfractionated heparin (UFH) is useful to reduce
ischemic events.†1–4
B-R
2. In patients with NSTE-ACS in whom an early
invasive approach is not anticipated, either
enoxaparin or fondaparinux are recommended
alternatives to UFH to reduce ischemic events.5–11
Anticoagulant Therapy in Patients Undergoing Coronary
Revascularization
1
C-LD
3. In patients with ACS undergoing coronary
revascularization (CABG or PCI) in the same
admission, parenteral anticoagulation should be
continued until revascularization to reduce
ischemic events.12,13
Anticoagulant Therapy to Support PCI in ACS (STEMI and
NSTE-ACS)
1
C-EO
4. In patients with ACS undergoing PCI, intravenous
UFH is useful to reduce ischemic events.†
1
B-R
5. In patients with STEMI undergoing PCI, bivalirudin
is useful as an alternative to UFH to reduce
mortality and bleeding.†14–19
2b
B-R
6. In patients with NSTE-ACS undergoing PCI,
bivalirudin may be reasonable as an alternative to
UFH to reduce bleeding.†16,20–23
2b
B-R
7. In patients with ACS, intravenous enoxaparin may
be considered as an alternative to UFH at the
time of PCI to reduce ischemic events.‡7,8,24–26
3: Harm
B-R
8. In patients with ACS, fondaparinux should not be
used to support PCI because of the risk of
catheter thrombosis.5,27
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Recommendations for Parenteral Anticoagulation (Continued )
COR
LOE
Recommendations
STEMI: Anticoagulant Therapy Treated With Fibrinolytic Therapy
1
A
9. In patients with STEMI treated with fibrinolytic
therapy, parenteral anticoagulation should be
continued for the duration of the hospital stay
(maximum of 8 days) or until revascularization is
performed to reduce ischemic events.9,10,27–29
1
A
10. In patients with STEMI treated with fibrinolytic
therapy who are not intended to undergo an
invasive approach, enoxaparin is the recommended
anticoagulant to reduce ischemic events.9,10,28,29
1
B-R
11. In patients with STEMI treated with fibrinolytic
therapy who are not intended to undergo an invasive approach, fondaparinux is a recommended
alternative to reduce ischemic events.27,30
*At the time of diagnosis and prior to invasive coronary angiography if planned.
†Adapted or
‡modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.”31
Synopsis
Parenteral anticoagulation is recommended for all patients with ACS, irrespective of the initial treatment
strategy, to treat the underlying pathophysiologic process (coronary atherothrombosis) and reduce the risk
of recurrent MACE (Table 10). Although eventual diagnostic reclassification can occur (ie, to other nonatherothrombotic ACS diagnoses such as coronary
spasm or other conditions that can mimic ACS, such
as stress cardiomyopathy or myocarditis), initial parenteral anticoagulation is intended to treat thrombus
caused by atherosclerotic plaque disruption (rupture or
erosion) in patients with presumed type 1 MI.32 Anticoagulation strategies are to be initiated upstream (at
the time of diagnosis and prior to coronary angiography) and to support PCI or other reperfusion therapy.
In patients with ACS undergoing PCI, intraprocedural
thrombin generation and platelet aggregation may
occur, for which reason parenteral anticoagulation is
recommended to reduce the risk for thrombotic complications.33 The choice of a parenteral anticoagulant
can be complex because it is influenced by various factors, including vascular access site, renal function, and
concomitant use of other antiplatelet or anticoagulant
agents. Heparin-induced thrombocytopenia can occur with both UFH and low-molecular-weight heparin;
in this context, argatroban and bivalirudin are direct
thrombin inhibitors that are acceptable alternative anticoagulants for patients with known heparin-induced
thrombocytopenia.34,35
Recommendation-Specific Supportive Text
1. UFH has traditionally been the preferred anticoagulant to treat patients with NSTE-ACS.1–4
However, limitations to its use include the lack of
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2025 Acute Coronary Syndromes Guideline
Table 10. Dosing of Parenteral Anticoagulation in ACS
Dosing
UFH
Initial therapy: Loading dose 60 IU/kg (max 4000 IU), with initial infusion 12 IU/kg per h (max 1000 IU/h) adjusted to therapeutic aPTT
range of 60-80 s.
To support PCI: In patients who have received prior anticoagulant therapy, additional UFH as needed to achieve an ACT 250-300 s.
In patients who have not received prior anticoagulant therapy, 70-100 U/kg initial bolus to achieve target ACT of 250-300 s.
With fibrinolytic therapy: Loading dose 60 IU/kg (maximum 4000 IU) with initial infusion 12 IU/kg per h (maximum 1000 IU/h) adjusted to
therapeutic aPTT range.
Bivalirudin
To support PCI: 0.75 mg/kg bolus, 1.75 mg/kg per h IV infusion during the PCI procedure.
Post-PCI infusion for PPCI: 1.75 mg/kg per h for 2-4 h post-PCI.
In patients with CrCl <30 mL/min, reduced infusion to 1 mg/kg per h.
Enoxaparin
Initial therapy: 1 mg/kg subcutaneous every 12 h. Reduce dose to 1 mg/kg per d subcutaneous if CrCl <30 mL/min.
To support PCI: For previous treatment with enoxaparin, if the last subcutaneous dose was administered 8-12 h earlier or if only 1 subcutaneous dose of enoxaparin has been administered, an IV dose of 0.3 mg of enoxaparin should be given. If the last dose was administered within
the previous 8 h, no additional enoxaparin should be given.
For patients who have not received prior anticoagulant therapy, 0.5-0.75 mg/kg IV bolus.
With fibrinolytic therapy: If age <75 y, 30 mg IV bolus, followed in 15 min by 1 mg/kg subcutaneous every 12 h (maximum 100 mg for the
first 2 doses).
If age ≥75 y: no bolus, 0.75 mg/kg subcutaneous every 12 h (maximum 75 mg for the first 2 doses).
Regardless of age, if CrCl <30 mL/min: 1 mg/kg subcutaneous every 24 h.
Fondaparinux
Initial therapy: 2.5 mg subcutaneous daily.
With fibrinolytic therapy: 2.5 mg IV, then 2.5 mg subcutaneous daily starting the following day. Contraindicated if CrCl <30 mL/min.
Fondaparinux should not be used to support PCI because of the risk of catheter thrombosis.
ACS indicates acute coronary syndromes; ACT, activated clotting time; aPTT, activated partial thromboplastin time; CrCl, creatinine clearance; PCI, percutaneous
coronary intervention; PPCI, primary percutaneous coronary intervention; and UFH, unfractionated heparin.
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a predictable dose response and risk of heparininduced thrombocytopenia.33 In unstable angina,
a meta-analysis including 1353 patients enrolled
from 6 randomized studies showed that, in comparison to patients treated with aspirin alone, those
treated with aspirin and heparin were at lower, albeit
nonstatistically significant, risk for MI or death during the randomized treatment period (relative risk,
0.67 [95% CI, 0.44-1.02]).3 Its efficacy compared
with placebo has not been evaluated in the current
era of dual antiplatelet therapy (DAPT) and early
revascularization.33
2. Fondaparinux, a synthetic pentasaccharide that
selectively binds antithrombin and causes rapid
and predictable inhibition of Factor Xa, was evaluated in patients with high-risk NSTE-ACS in the
OASIS-5 (Fifth Organization to Assess Strategies
in Acute Ischemic Syndromes) trial.5 Fondaparinux
was similar to enoxaparin in the risk for ischemic
events at 9 days, but it reduced major bleeding.
About 40% of the patients underwent PCI, and
an increase was observed in the rate of guidingcatheter thrombus formation with fondaparinux
(0.9% versus 0.3%) compared with enoxaparin. In
NSTE-ACS, despite some data favoring the use
of enoxaparin over UFH,11 multiple meta-analyses
have not demonstrated compelling superiority in
efficacy over UFH.7,26,36 A meta-analysis comparing
low-molecular-weight heparin to UFH in 12 171
patients with ACS without ST-segment elevation
across 5 randomized trials showed no significant
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difference in death or MI (2.2% versus 2.3%) or in
the risk of major bleeding.36
3. For patients with ACS undergoing coronary revascularization (CABG or PCI), parenteral anticoagulation is indicated until revascularization. The
premature discontinuation of anticoagulation is
associated with a transient rebound increase in
thrombin activity and activated protein C and the
reactivation of ischemic events,12,13 with the greatest risk for reinfarction in the first 4 to 8 hours after
the discontinuation of anticoagulation.
4. UFH has traditionally been the preferred anticoagulant to support PCI in patients with NSTE-ACS.
Activated clotting time is used to guide dosing during PCI.37 Although its pharmacokinetic effects are
not always predictable, its anticoagulant effect is
reversible with the administration of protamine.
5. Bivalirudin is a direct thrombin inhibitor evaluated
in both NSTE-ACS and STEMI that can be used
to support PCI. In the BRIGHT-4 (Bivalirudin with
Prolonged Full-Dose Infusion during PPCI versus
Heparin) trial,15 which enrolled patients with STEMI
undergoing PPCI using radial access (93%), bivalirudin was compared with heparin monotherapy in
an open-label design. The bivalirudin regimen used
included the standard bolus and dosing (0.75 mg/kg,
then 1.75 mg/kg per hour) plus a post-PCI infusion at the full dose (1.75 mg/kg per hour) for
2 to 4 hours. Bivalirudin with the full dose postPCI infusion was superior to UFH in reducing the
30-day composite of all-cause death or BARC
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(Bleeding Academic Research Consortium) types
3-5 bleeding (4.39% versus 3.06%; P =0.007).15
All-cause death was also reduced with bivalirudin
(3.92% versus 2.96%; P =0.04), as well as 30-day
stent thrombosis (0.37% versus 1.1%; P =0.0015).
Based on these results, when bivalirudin is used
to support PPCI for STEMI, a postprocedure 2- to
4-hour infusion at full dose is recommended.15,38,39
6. Meta-analyses comparing bivalirudin versus UFH
with or without glycoprotein IIb/IIIa inhibitors in
patients with ACS demonstrate that bivalirudin
is associated with a lower risk for major bleeding.16,17,40 In the context of NSTE-ACS, bivalirudin was evaluated in the ACUITY (A Comparison
of Angiomax Versus Heparin in Acute Coronary
Syndromes) trial, where bivalirudin was noninferior to UFH plus glycoprotein IIb/IIIa inhibitor
for the risk of MACE and superior with respect
to 30-day major bleeding.41 The bleeding definition used in the study was specific to the
ACUITY trial. Bivalirudin was also evaluated in
the MATRIX (Minimizing Adverse Hemorrhagic
Events by Transradial Access Site and Systemic
Implementation of AngioX) trial where it was compared against UFH alone (ie, without concomitant
glycoprotein IIb/IIIa inhibitor).42 No significant difference was observed between the 2 arms with
respect to 30-day ischemic or bleeding events.
7. Intravenous enoxaparin compared with UFH
reduces the risk for ischemic outcomes without a
significant difference in bleeding in the setting of
PPCI. In the ATOLL (Acute Myocardial Infarction
Treated with Primary Angioplasty and Intravenous
Enoxaparin or Unfractionated Heparin to Lower
Ischemic and Bleeding Events at Short- and Longterm Follow-up) trial,24 which enrolled patients
presenting with STEMI, the primary endpoint of
30-day incidence of death, complication of MI,
procedural failure, or major bleeding occurred in
28% of patients with enoxaparin compared with
34% with UFH (P =0.06). Although the incidence
of primary endpoint was not significantly different
between enoxaparin and UFH, the secondary endpoint of 30-day death, recurrent ACS, or urgent
revascularization was significantly lower in the
enoxaparin group (7% versus 11%; P =0.015). In
addition, a net clinical benefit (death, complication
of MI, or major bleeding) was observed with enoxaparin compared with UFH (10% versus 15%;
P =0.03). In a meta-analysis of 10 451 patients,
intravenous enoxaparin was associated with a significant reduction in death and major bleeding.26
8. Fondaparinux should not be used as the sole anticoagulant to support PCI because of the risk of catheter
thrombosis.5,27,31 In the OASIS-5 trial, an increase was
observed in the rate of catheter-related thrombus
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with fondaparinux compared with enoxaparin (0.9%
versus 0.4%).5 Similar results were observed in the
OASIS-6 (The Safety and Efficacy of Fondaparinux
versus Control Therapy in Patients with STEMI) trial
in which a higher rate of guiding-catheter thrombosis
and more coronary complications with fondaparinux
were observed when used during PCI.27
9. In patients with STEMI treated with fibrinolytic
therapy, parenteral anticoagulation is recommended before and after fibrinolytic therapy to
reduce ischemic events. In studies of fibrinolytic
therapy such as the GUSTO (Global Utilization of
Streptokinase and Tissue Plasminogen Activator for
Occluded Coronary Arteries) trial, the ASSENT-3
(Assessment of the Safety and Efficacy of a New
Thrombolytic Regimen) trial, or the ExTRACT-TIMI
25 (Enoxaparin and Thrombolysis Reperfusion
for Acute Myocardial Infarction TreatmentThrombolysis in Myocardial Infarction 25) study,
intravenous heparin was administered for at least
48 hours.10,29,43 In the ExTRACT-TIMI 25 study,
the UFH infusion was given for at least 48 hours
but could be continued for a longer period at the
treating physician’s discretion, whereas the subcutaneous injections of enoxaparin were continued until hospital discharge or for a maximum of 8
days (whichever came first).10 Patients randomized
to enoxaparin had a lower risk of death or nonfatal recurrent MI through 30 days compared with
UFH (9.9% versus 12.0%); however, treatment
with enoxaparin was associated with an increase
in major bleeding (2.1% versus 1.4%).10
10. In patients with STEMI who received fibrinolytic
therapy and who are not planned for an invasive
approach, enoxaparin is the preferred anticoagulant over UFH.9,10,28,29,44 In the ExTRACT-TIMI 25
study, enoxaparin until hospital discharge or for
a maximum of 8 days (whichever came first) was
compared with UFH administered for at least 48
hours (could be continued for a longer period at the
treating physician’s discretion) in 20 506 patients
with STEMI receiving fibrinolytic therapy.10 The
primary endpoint of death or nonfatal recurrent MI
through 30 days occurred in 12% in the UFH group
compared with 9.9% in the enoxaparin group. In
a meta-analysis of 14 randomized trials, UFH did
not reduce reinfarction or death in patients treated
with fibrinolytic therapy. In contrast, low-molecularweight heparin reduced the risk of reinfarction
and death compared with placebo and the risk of
reinfarction.45
11. In patients with STEMI who are not likely to undergo
an invasive approach, fondaparinux is an alternate
anticoagulant that can be used. In the OASIS-6
trial of patients with STEMI who were treated with
thrombolytic agents (predominantly streptokinase),
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2025 Acute Coronary Syndromes Guideline
4.5. Lipid Management
Recommendations for Lipid Management
Referenced studies that support recommendations are summarized
in the Evidence Table.
COR
LOE
Recommendations
1
A
1. In patients with ACS, high-intensity statin therapy
is recommended to reduce the risk of MACE.*1–4
A
2. In patients with ACS who are already on
maximally tolerated statin therapy with lowdensity lipoprotein cholesterol (LDL-C)
≥70 mg/dL (≥1.8 mmol/L), adding a nonstatin
lipid-lowering agent is recommended to further
reduce the risk of MACE.†5–7
B-R
3. In patients with ACS who are statin intolerant,
nonstatin lipid-lowering therapy is recommended
to lower LDL-C and reduce the risk of MACE.8–10
2a
B-R
4. In patients with ACS who are already on
maximally tolerated statin therapy with LDL-C
55 to 69 mg/dL (≥1.4 to <1.8 mmol/L), adding
a nonstatin lipid-lowering agent is reasonable to
reduce the risk of MACE.*5–7,11–13
2b
B-R
5. In patients with ACS, the concurrent initiation of
ezetimibe in combination with maximally tolerated
statin may be considered to reduce the risk of
MACE.5
1
1
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*Modified or
†adapted from the “2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline
for the Management of Patients With Chronic Coronary Disease.”14
Synopsis
The current recommendations focus on patients with
recent (ie, within 12 months) ACS. The 2023 AHA/
ACC/ACCP/ASPC/NLA/PCNA CCD guideline provides more detailed recommendations on long-term
management of lipids in patients with prior ACS.14
ASCVD event rates are substantially higher in patients
with recent ACS than those with CCD, with 1-year
rates of cardiovascular death, MI, and ischemic stroke
estimated at 10% to 15% after an ACS hospitalization.15,16 Higher risk among patients with ACS supports
more aggressive LDL-cholesterol (LDL-C) targets in patients with recent ACS compared with those with CCD
(Figure 5).14–16 RCTs have demonstrated ASCVD event
reduction with multiple different pharmacological approaches to LDL-C level lowering, with the magnitude
of benefit proportional to the degree of LDL-C level lowering.17 In patients with ACS, RCTs have demonstrated
incremental benefit with high- compared with moderateintensity statin therapy in regard to reduction in MACE.1–4
For patients who do not reach LDL-C treatment goals
on maximally tolerated statin therapy, or who are intolerant to statins, several nonstatin therapies, including
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
ezetimibe, monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9), and bempedoic
acid, can both lower LDL-C levels and improve ASCVD
outcomes across diverse populations.5–10 Inclisiran also
lowers LDL-C levels by preventing translation of PCSK9
mRNA, but clinical outcomes studies are not yet available (Table 12). Nonetheless, the relative benefit of
LDL-C–lowering therapies is expected to be proportional
to the observed reduction in LDL-C levels (Tables 11
and 12).5–11 A lipid profile is recommended as soon as
feasible after presentation with ACS (Figure 5), because
LDL-C levels decrease modestly beginning 24 hours
from symptom onset.18 Lipid management after hospital
discharge is discussed in Section 11.2, “Reassessment
of Lipid Levels Postdischarge.”
Recommendation-Specific Supportive Text
1. High-intensity statin regimens lower LDL-C concentration by an average of ≥50% (Table 11). The
CTT (Cholesterol Treatment Trialists) meta-analysis of 5 RCTs showed that LDL-C concentration
lowering with high-intensity statins compared with
moderate-intensity statins reduces major vascular events by approximately 15% in patients with
coronary artery disease (CAD).4 An individual participant meta-analysis of the A to Z (Aggrastat to
Zocor) and PROVE IT (Pravastatin or Atorvastatin
Evaluation and Infection Therapy)-TIMI 22 trials,
both of which were performed in patients stabilized early after ACS, demonstrated significant
reductions in cardiovascular and all-cause death
with more intensive versus less intensive statin
regimens.19 The benefit of a high-intensity statin
regimen appears early after ACS and persists over
time.3 The benefit of high-intensity statins after
ACS appears to be independent of baseline LDL-C
concentration. No indication was observed of any
safety concerns from achieving very low LDL-C
concentrations on statins or other lipid-lowering
therapies; therefore, high-intensity statin therapy
should not be de-escalated during follow-up in
patients who are tolerating treatment.13
2. Multiple therapeutic options are now available
to add to maximally tolerated statin therapy to
achieve desired LDL-C goals in patients with ACS
(Table 12). In IMPROVE IT (Improved Reduction
of Outcomes; Vytorin Efficacy International Trial),
addition of ezetimibe to simvastatin 40 mg daily
in patients <10 days after ACS led to a modest
but significant reduction in MACE, over a median
follow-up of 6 years.5 Clinical trials of PCSK9
inhibitors have demonstrated a 15% relative risk
reduction in MACE over a median of 2 to 3 years
including patients >1 month after ACS.6,7,20 Greater
absolute benefit with PCSK9 inhibitors has been
TBD TBD, 2025
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AND GUIDELINES
fondaparinux significantly reduced the risk of the
primary endpoint of death or reinfarction at 30
days, including a significant reduction in mortality,
reinfarction, and severe bleeding when compared
with placebo or UFH.27,30
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CLINICAL STATEMENTS
AND GUIDELINES
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Figure 5. Management of Lipid-Lowering Therapy for Patients With ACS.
Colors correspond to Class of Recommendation in Table 2.
*Nonstatin LDL-lowering therapy: ezetimibe, PCSK9 inhibitor (alirocumab, evolocumab and inclisiran), and/or bempedoic acid.
ACS indicates acute coronary syndromes; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; and PCSK9, proprotein
convertase subtilisin/kexin type 9.
demonstrated in those patients enrolled closer
to their ACS event.20,21 Evolocumab effectively
reduces LDL-C levels early after ACS and has
demonstrated favorable changes on plaque components by intracoronary imaging in patients with
NSTEMI.22–24 Greater plaque regression has also
been reported by intracoronary imaging for patients
treated with alirocumab after AMI.25 Inclisiran is a
small interfering RNA targeting synthesis of the
PCSK9 protein that is administered at 6-month
intervals after an initial 3-month dose. Inclisiran
lowers LDL-C levels by approximately 50% and
is well tolerated,26 but clinical outcome studies are
not yet available. Bempedoic acid works upstream
from statins in the liver and leads to approximately
20% reduction in LDL-C levels. It reduces MACE
Table 11. Nonstatin Treatment Options for LDL-C Lowering in Patients With ACS Who Are Not at LDL-C Goal on Maximally
Tolerated Statin Therapy
Drug
Mechanism of Action
LDL-C Lowering (%)
Outcomes Study Performed in Patients
With Recent ACS?
Potential Adverse Effects
Ezetimibe*
Blocks NPC1L1 cholesterol absorption
15-25
Yes (<10 d post ACS)
Hyperuricemia
Evolocumab
Monoclonal antibody to PCSK9
∼60
Established ASCVD (>1 mo post ACS)
Injection site reaction
Alirocumab
Monoclonal antibody to PCSK9
∼60
Yes (1-12 mo post ACS)
Injection site reaction
Inclisiran
Inhibitor of PCSK9 synthesis (small
interfering RNA)
∼50
Clinical outcomes trials in ASCVD are
ongoing
Injection site reaction
Bempedoic acid†
ATP-citrate lyase inhibitor
∼20
With or at high risk for CVD (>90 d post
ACS)
Gout; gallstones; liver
function test abnormalities
All agents are approved by the FDA.
*The LDL-C lowering potency of ezetimibe is greater when used in combination with statin therapy (approximately 25% LDL-C reduction) than when used as monotherapy (15%-20%).
†Coadministration of bempedoic acid with simvastatin at a dose >20 mg and pravastatin at a dose >40 mg is not recommended due to the increased risk of musclerelated adverse effects from statins.
ACS indicates acute coronary syndromes; ASCVD, atherosclerotic cardiovascular disease; CVD, cardiovascular disease; FDA, US Food and Drug Administration; LDLC, low-density lipoprotein cholesterol; NPC1L1, Niemann-Pick C1-Like 1 protein; and PCSK9, proprotein convertase subtilisin/kexin type 9.
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2025 Acute Coronary Syndromes Guideline
Table 12. Statin Classification
High-Intensity Therapy*
Moderate-Intensity
Therapy†
Low-Intensity Therapy‡
Atorvastatin 40-80 mg
Atorvastatin 10-20 mg
Simvastatin 10 mg
Rosuvastatin 20-40 mg
Rosuvastatin 5-10 mg
Pravastatin 10-20 mg
Simvastatin 20-40 mg
Lovastatin 20 mg
Pravastatin 40-80 mg
Fluvastatin 20-40 mg
Lovastatin 40 mg
Fluvastatin XL 80 mg
Fluvastatin 40 mg BID
Pitavastatin 1-4 mg
Modified with permission from Grundy et al.42 Copyright 2018 American Heart
Association, Inc., and American College of Cardiology Foundation.
*Expected LDL-C reduction ≥50%.
†Expected LDL-C reduction ≥30% to 49%.
‡Expected LDL-C reduction <30%.
BID indicates twice daily; LDL-C, low-density lipoprotein cholesterol.
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by 13% in statin-intolerant patients when started
>90 days after ACS.10
3. Statin intolerance is frequent in clinical practice
and the most commonly reported cause is statinassociated muscle symptoms.27 To consider a
patient as having statin intolerance, a minimum of
2 statins should be attempted, including at least
1 at the lowest approved daily dose.28 Currently
available options for patients with complete or
partial intolerance to statin therapy include ezetimibe, PCSK9 inhibitor monoclonal antibodies,
inclisiran, and bempedoic acid. Ezetimibe and
PCSK9 inhibitors have been demonstrated to be
safe and well tolerated and improve lipid parameters in statin-intolerant patients.8,9 However,
outcomes studies using these agents as monotherapy or in combination in statin-intolerant
patients are not available. Bempedoic acid is an
ATP citrate lyase inhibitor that reduces LDL-C
levels by 15% to 25% with low rates of musclerelated adverse effects.29,30 A combination product that combines bempedoic acid with ezetimibe
lowered LDL-C levels by approximately 35%.31
In the CLEAR Outcomes (Cholesterol Lowering
via Bempedoic Acid, an ACL-Inhibiting Regimen)
trial, bempedoic acid was compared with placebo
in statin-intolerant patients with or at high risk for
ASCVD. Patients with ACS within 90 days prior
to randomization were excluded from this trial.
Mean LDL-C level was 139 mg/dL at enrollment
and was reduced by 29 mg/dL with bempedoic
acid compared with placebo. MACE was reduced
by 13% in the bempedoic acid arm. Bempedoic
acid raised uric acid levels in a small subset of
patients, and rates of abnormal liver function
tests, gout, and gallstones were increased with
its use in the trial.10
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CLINICAL STATEMENTS
AND GUIDELINES
Statin Classification by Expected LDL-C Reduction
4. IMPROVE IT randomized patients post-ACS with
LDL-C levels of ≥50 mg/dL and ≤125 mg/dL
(≤100 mg/dL if on lipid-lowering therapy) to the
combination of simvastatin (40 mg) and ezetimibe (10 mg) or simvastatin (40 mg) and placebo
(simvastatin monotherapy), with median LDL-C
level at enrollment of 69.5 mg/dL. The addition
of ezetimibe reduced the relative risk of MACE
by 6.4% compared with placebo.5 Benefit was
similar among patients with baseline LDL-C 50
to 70 mg/dL versus ≥70 mg/dL.32 FOURIER
(Further Cardiovascular Outcomes Research
With PCSK9 Inhibition in Subjects With Elevated
Risk) and ODYSSEY OUTCOMES (Evaluation
of Cardiovascular Outcomes After an Acute
Coronary Syndrome During Treatment With
Alirocumab) enrolled patients with LDL-C ≥70
mg/dL and thus did not specifically assess outcomes associated with adding PCSK9 inhibitor
therapy among patients with LDL-C levels 55
to 70 mg/dL.6,7 However, secondary analyses
of both trials demonstrated better outcomes in
patients with achieved LDL-C <50 mg/dL versus
those with achieved LDL-C levels ≥50 mg/dL,
with monotonic relationships, suggesting better
outcomes with progressively lower LDL-C even
well below 50 mg/dL.11,12 Rates of neurocognitive
and muscle events, including hemorrhagic stroke,
were not increased among patients who achieved
very low LDL-C levels with PCSK9 inhibition.11,12
Longer term follow-up studies support continued
benefit and safety associated with achieving and
maintaining very low LDL-C levels in secondary
prevention with a PCSK9 inhibitor over several
years.33 The benefits of ezetimibe and PCSK9
inhibitors appear to be greater among higher risk
patients with prior ACS and diabetes or more
advanced coronary or polyvascular disease or
elevated biomarkers.20,34–41
5. Ezetimibe reduces LDL-C levels by 15% to 25%
by blocking its absorption from the gastrointestinal tract via the Niemann-Pick C1-Like 1 protein
(NPC1L1). The IMPROVE IT trial studied the combination of simvastatin (40 mg) and ezetimibe (10
mg) (simvastatin-ezetimibe) to simvastatin (40
mg) and placebo (simvastatin monotherapy) in
patients hospitalized with an ACS in the past 10
days. The median time from ACS to randomization
was 5 days, and 34% of patients were already on
a statin at the time of the ACS event. The addition
of ezetimibe reduced the relative risk of MACE by
6.4% compared with placebo (hazard ratio, 0.936
[95% CI, 0.89-0.99]) over a median of 6 years’ follow-up. Ezetimibe was well-tolerated without any
clear imbalances in adverse events compared with
placebo.5
CLINICAL STATEMENTS
AND GUIDELINES
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2025 Acute Coronary Syndromes Guideline
4.6. Beta-Blocker Therapy
but increased the risk of cardiogenic shock that
occurred mainly during the first 24 hours.1 In a
small open-label trial of 801 patients with STEMI
who underwent PPCI, carvedilol did not reduce
MACE over 3 years, but the trial was underpowered to detect a difference.8 Overall, the weight
of the evidence suggests that a low dose of oral
beta blocker should be initiated in patients without
contraindication early after diagnosis of ACS (<24
hours) with slow dose escalation as blood pressure
and heart rate permit. Use should be discontinued
in those with new or worsening HF symptoms or
signs of cardiogenic shock. In hemodynamically
stable patients with STEMI who do not have acute
HF, intravenous beta blockers can be administered
prior to reperfusion if there are ongoing symptoms
or a clinical indication for administration. The weight
of the evidence does not support the routine use of
intravenous beta blockers prior to PPCI because of
inconsistent results as to whether it has any favorable effect on infarct size or clinical outcomes.9,10
The optimal duration of beta-blocker use remains
unclear in patients with preserved LVEF. Although
a randomized trial did not confirm long-term benefit
from continued use of a beta blocker after hospital
discharge in lower risk patients with preserved LV
function who had undergone coronary revascularization,7 additional studies are ongoing in this space.
Recommendation for Beta-Blocker Therapy
Referenced studies that support recommendation are summarized
in the Evidence Table.
COR
LOE
Recommendation
1
A
1. In patients with ACS without contraindications, early
(<24 hours) initiation of oral beta-blocker therapy
is recommended to reduce risk of reinfarction and
ventricular arrhythmias.1–5
Synopsis
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Beta blockers decrease myocardial oxygen demand by
reducing the heart rate, blood pressure, and myocardial
contractility.1,3 The clinical benefit of beta blockers in patients with left ventricular ejection fraction (LVEF) <40%
and stabilized HF is well established, including patients
post-MI.3–5 Most of the RCT data pertaining to early use
of beta-blocker therapy in STEMI were conducted in the
pre-reperfusion era.3 No adequately powered RCTs have
been done that examine the clinical benefit of beta blockers during hospitalization among patients exclusively with
NSTE-ACS. Although most studies were conducted in patients with STEMI, early hospital initiation of beta-blocker
therapy (within 24 hours) is recommended among most
patients with ACS and without contraindications (eg,
acute HF [Killip class II-IV], evidence of low cardiac output
state or at risk for cardiogenic shock, PR interval >0.24
milliseconds, second- or third-degree heart block without
a cardiac pacemaker, severe bradycardia, active bronchospasm).1,2,6 Patients with an initial contraindication to
beta-blocker therapy on presentation can be reassessed
after 24 hours and initiated on oral beta-blocker therapy
if the initial contraindication has resolved. Further study is
warranted to examine the benefit in those patients with
NSTE-ACS. Although an open-label randomized trial has
raised questions about the benefit of long-term betablocker therapy following hospital discharge in patients
with ACS who have undergone coronary revascularization and have preserved left ventricular (LV) function,7 this
area remains under study.
Recommendation-Specific Supportive Text
1. RCTs from both the pre-reperfusion era and in
the early reperfusion era have shown that early
initiation of beta-blocker therapy reduces the risk
of reinfarction and ventricular arrhythmias among
patients with STEMI.1–3 The COMMIT (Clopidogrel
and Metoprolol in Myocardial Infarction) trial
included 45 852 patients (approximately 50%
received fibrinolytic therapy and 7% having NSTEACS) and showed that early initiation of high doses
(ie, up to 15 mg intravenously then 200 mg orally
daily) of metoprolol reduced the risk of reinfarction
and ventricular fibrillation compared with placebo
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4.7. Renin-Angiotensin-Aldosterone System
Inhibitors
Recommendations for Renin-Angiotensin-Aldosterone System
Inhibitors
Referenced studies that support recommendations are summarized
in the Evidence Table.
COR
LOE
Recommendations
1
A
1. In high-risk patients with ACS (LVEF ≤40%,
hypertension, diabetes mellitus, or STEMI with
anterior location), an oral angiotensin-converting
enzyme inhibitor (ACEi) or an angiotensin
receptor blocker (ARB) is indicated to reduce
all-cause death and MACE.1–6
1
B-R
2. In patients with ACS and LVEF ≤40%, and
with HF symptoms and/or diabetes mellitus, a
mineralocorticoid receptor antagonist is indicated
to reduce all-cause death and MACE.7
2a
A
3. In patients with ACS who are not considered high
risk, an oral ACEi or an ARB is reasonable to
reduce MACE.4
Synopsis
Oral ACE inhibitors reduce all-cause death and MACE in
patients with STEMI or NSTEMI, particularly when associated with high-risk features (LVEF ≤40%, hypertension,
diabetes mellitus, or STEMI with anterior location).1–4,6 Even
in AMI without high-risk features, use of an oral ACEi
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or hyperkalemia (serum potassium >5.0 mmol/L)
were excluded from enrollment.7 In a trial of 1012
patients with acute STEMI and without a history of
HF, the use of eplerenone reduced the primary endpoint compared with placebo, but the benefit was
largely driven by a reduction in natriuretic peptides.11
3. The ACE Inhibitor Myocardial Infarction
Collaborative Group meta-analysis of 98 496
patients with AMI reported a 30-day mortality rate
of 7.1% in AMI patients treated with an ACEi compared with 7.6% receiving placebo (proportional
reduction, 7% [95% CI, 2-11]; P =0.004), and the
benefit appeared to be irrespective of baseline
risk.4 The use of an ACEi also reduced nonfatal
cardiac failure compared with placebo.4
5. STEMI MANAGEMENT: REPERFUSION
STRATEGIES
5.1. Regional Systems of STEMI Care
Recommendation for Regional Systems of STEMI Care
Referenced studies that support recommendation are summarized in
the Evidence Table.
COR
LOE
Recommendation
B-NR
1. All communities should create and maintain regional
systems of STEMI care that coordinate prehospital
and hospital-based STEMI care processes with the
goal of reducing total ischemic time and improving
survival in patients with STEMI.1–6
Recommendation-Specific Supportive Text
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1. Randomized controlled trials have demonstrated
a reduction in all-cause death and MACE with
the addition of an oral ACEi in patients with AMI
with LVEF ≤40%1,3 and in patients with anterior
STEMI.2 An individual-patient meta-analysis of
98 496 patients with AMI also showed a survival
benefit with ACEi use, with the greatest absolute
benefit in patients with hypertension, diabetes,
and STEMI of anterior location.4 In the VALIANT
(Valsartan in Acute Myocardial Infarction) trial of
patients with AMI with LV systolic dysfunction and/
or HF symptoms, the use of an ARB was statistically noninferior to an ACEi, and rates of all-cause
death were similar between the 2 treatment arms.5
Concomitant initiation of both an ACEi and ARB
in patients with AMI should be avoided due to an
increase in adverse events without added benefit
compared with either drug alone.5,8
2. In the EPHESUS (Eplerenone Post-Acute
Myocardial Infarction Heart Failure Efficacy and
Survival Study) trial, the mineralocorticoid receptor antagonist eplerenone reduced both all-cause
death and MACE during a mean follow-up of 16
months in patients with AMI with LVEF ≤40% who
also had symptoms of HF and/or diabetes mellitus. The use of evidence-based therapies for this
population was relatively high, including 86% use
of ACEi or ARB and 75% use of a beta blocker
at enrollment.7 Patients with advanced chronic
kidney disease (serum creatinine >2.5 mg/dL)
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1
Synopsis
The goal of optimizing outcomes after STEMI depends
not only on the efficient execution of STEMI care processes but also on the seamless communication and coordination of care among the teams caring for the patient.
The goal of each community is therefore to ensure a coordinated response to every patient with STEMI, regardless of physical location at presentation, to help minimize
total ischemic time. The creation and maintenance of
successful systems of STEMI care require detailed mapping of care for all possible routes by which a patient with
STEMI could present for diagnosis and receive definitive
reperfusion therapy at both PCI-capable and non–PCIcapable facilities, as well as access to cardiac surgical
care and other advanced care modalities (Figure 6).
The many stakeholders of regional systems of STEMI
care (including hospitals, EMS companies, regional public
health departments, and local governments) must ensure
that all components of a STEMI system of care function
in a coordinated way with no gaps in care processes to
help optimize STEMI outcomes in the community.
Recommendation-Specific Supportive Text
1. The establishment of coordinated regional systems
of STEMI care is associated with reduced time to
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confers a modest survival benefit.4 Compared with ACEi,
the benefits of an ARB in patients with AMI with HF or
LV systolic dysfunction are similar.5 Thus, in the absence
of contraindications, either an oral ACEi or ARB should
be initiated in appropriate patients with AMI.5,8 In patients
with AMI with LVEF ≤40%, and with HF symptoms and/
or diabetes mellitus, the addition of a mineralocorticoid
receptor antagonist reduced all-cause death and MACE
and should be given in the absence of advanced chronic
kidney disease, hyperkalemia, or other contraindication.
In patients with symptomatic HF and reduced LVEF,
sacubitril-valsartan has been demonstrated to be superior to an ACEi for reducing cardiovascular death or HF
hospitalization; however, the trial excluded patients within
3 months of ACS.9 In a trial of patients early after MI with
LVEF ≤40% and/or pulmonary congestion, sacubitril-valsartan did not significantly reduce cardiovascular death or
incident HF compared with an ACEi. Hypotensive events
were more common with sacubitril-valsartan, but no other
safety concerns were observed. Therefore, if treatment
with sacubitril-valsartan for HF with reduced ejection
fraction is planned, initiation of this combination agent
instead of an ACEi or ARB early after MI appears safe.10
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AND GUIDELINES
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Figure 6. Care System Pathway for Patients Experiencing Ischemic Symptoms Suggestive of ACS.
Systems of STEMI care, and the most common routes by which patients present for diagnosis and definitive reperfusion therapy for STEMI. Best
clinical practice consists of patients calling 9-1-1 (or other emergency services) to activate EMS; EMS obtaining a prehospital ECG, activating
the cardiac catheterization laboratory from the field for suspected STEMIs, and transporting the patient to the nearest PCI center when possible;
and achieving a system goal of FMC-to-device time within 90 minutes. Colors correspond to Class of Recommendation in Table 2. *Patients
with chest tightness or other symptoms indicative of a heart attack. ACS indicates acute coronary syndromes; ED, emergency department;
EMS, emergency medical services; FMC, first medical contact; PCI, percutaneous coronary intervention; PPCI, primary percutaneous coronary
intervention; and STEMI, ST-segment elevation myocardial infarction.
reperfusion and increased survival in STEMI in several
pre- versus postimplementation comparison studies
throughout the world.1–6 Over the past 15 years, considerable gains have been made in reducing FMC to
reperfusion times in patients with STEMI and these
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improvements in reperfusion times have been associated with improved outcomes.5,7 Unfortunately,
recent declines have been reported in the rates of
achieving established STEMI performance measures,8 in part due to the COVID-19 pandemic and
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5.2. Reperfusion at PCI-Capable Hospitals
5.2.1. PPCI in STEMI
Recommendations for PPCI in STEMI
Referenced studies that support recommendations are summarized
in the Evidence Table.
COR
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LOE
Recommendations
A
1. In patients with STEMI presenting <12 hours
after symptom onset, PPCI should be performed
with a goal of FMC to device activation of ≤90
minutes, or ≤120 minutes in patients requiring
hospital transfer, to improve survival.1–7
1
B-R
2. In patients with ACS and cardiogenic shock or
hemodynamic instability, emergency
revascularization of the culprit vessel by PCI or
CABG is indicated to improve survival,
irrespective of time from symptom onset.8–11
2a
B-NR
3. In patients with STEMI presenting 12 to 24 hours
after symptom onset, PPCI is reasonable to
improve clinical outcomes.*12–15
C-LD
4. In patients with STEMI presenting >24 hours after
symptom onset with the presence of ongoing
ischemia or life-threatening arrhythmia, PPCI is
reasonable to improve clinical outcomes.†12,14
B-R
5. In patients who are stable with STEMI who have
a totally occluded infarct-related artery >24 hours
after symptom onset and are without
evidence of ongoing ischemia, acute severe HF,
or life-threatening arrhythmia, PPCI should not be
performed due to lack of benefit.†16,17
1
2a
3: No
Benefit
*Reproduced or
†modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery
Revascularization.”18
Synopsis
Timely PPCI confers improved survival compared with fibrinolytic therapy as primary reperfusion therapy for patients
with STEMI.6,7 Systems of care designed to reduce the time
to PPCI for patients with STEMI have been consequential
in reducing risk of early death.19,20 The goal is to provide
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PPCI as soon as possible after the diagnosis of STEMI is
made with first device activation within 90 minutes from
FMC among walk-in and EMS-transported patients and
120 minutes for transfer patients from non–PCI-capable
facilities.1–7 The benefit of PPCI begins to diminish for
those >12 hours from symptom onset, but there appears
to be continued benefit for PPCI through approximately 24
hours.12,13 In stable asymptomatic patients with an occluded artery >48 hours after symptom onset, routine PCI has
not been shown to be beneficial in the absence of ongoing
ischemia; the relative utility of routine PCI for asymptomatic
patients with STEMI between 24 to 48 hours from symptom onset is less rigorously tested.14,15 However, coronary
revascularization should be considered for patients with
late presentations with continued signs and symptoms of
ischemia, including cardiogenic shock, acute severe HF,
persistent angina, and life-threatening arrhythmias.
Recommendation-Specific Supportive Text
1. PPCI is the recommended reperfusion therapy in
patients with STEMI and ischemic symptoms when
performed ≤90 minutes (FMC–to–first-device
activation) or ≤120 minutes in transfer patients to
improve survival.1–7 The success of PPCI in achieving these goals was facilitated by the introduction
in 2006 of the AHA’s Mission: Lifeline programs
involving EMS and clinicians (eg, emergency medicine, cardiology, nursing) with practiced drill-down
programs and regionalization of care21 that have
improved myocardial salvage, as well as reduced risk
of death and adverse outcomes.4,22,23 PPCI is superior
to fibrinolytic therapy, which is used when the patient
is in a non–PCI-capable hospital and transfer time
to a PCI-capable hospital is anticipated to be >120
minutes. Compared with fibrinolytic therapy with a
similar treatment delay, PPCI offers higher rates of
infarct-related artery patency, and restoring TIMI 3
epicardial flow grade, as well as lower rates of recurrent ischemia, reinfarction, emergency repeat revascularization procedures, intracranial hemorrhage, and
death.6,7 Radial access for PPCI has further reduced
death, decreased access site bleeding, decreased
the need for transfusion, and reduced acute kidney
injury when compared with femoral access (Section
7.1, “Vascular Access Approach for PCI”).24,25
2. In the SHOCK (Should We Emergently Revascularize
Occluded Coronaries for Cardiogenic Shock) trial,9
reported in 1999, patients with AMI and cardiogenic
shock were randomized to medical therapy or emergency revascularization. Among the patients randomized to revascularization, 64% of patients were
referred for PCI and 36% for CABG surgery. The
median time from randomization to revascularization was 0.9 hours for PCI and 2.7 hours for CABG
surgery. Despite lack of a significant difference in
TBD TBD, 2025
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AND GUIDELINES
related challenges in ensuring adequate resourcing and staffing of EMS agencies and hospitals.
Therefore, all communities should continue to establish, reinvigorate, and maintain regional systems of
STEMI care to improve outcomes of patients with
STEMI globally. The collection of high-quality data at
every stage of care is an inseparable component of
a STEMI system of care. Successful STEMI systems
have robust mechanisms for (1) educating the public of the need to immediately call 9-1-1 (or other
appropriate local emergency services) for ischemic
symptoms and not driving themselves to the nearest
hospital; (2) data collection that balances the need
for adequate data capture without introducing data
overburden; (3) data sharing within hospital departments (eg, ED and cardiology) or between hospitals
and EMS agencies; and (4) meetings to review and
discuss shared data at local and system levels to
drive process improvement.
CLINICAL STATEMENTS
AND GUIDELINES
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the primary endpoint of mortality at 30 days, emergency revascularization with either PCI or CABG
surgery reduced mortality at 6 months,9 and the
mortality rate benefit was maintained through 1 and
6 years.26,27 In an observational analysis from the
FITT-STEMI (Feedback Intervention and Treatment
Times in ST-Elevation Myocardial Infarction) trial,
for every 10-minute delay in PPCI after 60 minutes
from FMC, there were an additional 3 to 4 deaths
per 100 with >80% mortality beyond 6 hours of
delay from FMC for patients with cardiogenic shock.8
Therefore, it is recommended that PPCI should be
performed in patients with STEMI and cardiogenic
shock as soon as possible, ideally within 90 minutes,
to reduce the mortality rate. Observational studies
suggest that emergency CABG surgery remains a
treatment option in patients with cardiogenic shock
who are not amenable to primary reperfusion with
PCI10,11 or when PCI is not successful.11,28
3. The benefit of PCI for asymptomatic patients presenting 12 to 24 hours after symptom onset is not
well studied. Small randomized trials of patients 12
to 48 hours after symptom onset in STEMI have
demonstrated that PPCI reduces infarct size and
improves the LVEF.12,14 These findings are further
supported by observational data.13,15
4. No dedicated trials have been done that examine the
benefit of PPCI in patients with STEMI presenting
late >24 hours after symptom onset who have clinical evidence of ongoing ischemia, acute severe HF,
or life-threatening arrhythmias. Observational data
and small trials suggest that PCI in patients with
STEMI with delayed presentations is reasonable
and is associated with improved outcomes.12,14,15
5. PCI is not recommended for an occluded infarctrelated artery if the patient is asymptomatic and has
a completed infarct. MACE outcomes were similar in
those with an occluded infarct-related artery versus
those who underwent PCI 3 to 28 days after an MI
(Occluded Artery Trial [OAT])16 and results were no
different at 7 years follow-up.29 Similar findings were
noted in the DECOPI (Desobstruction Coronaire en
Post-Infarctus) trial, which enrolled patients with an
occluded artery and Q waves on the ECG presenting 2 to 15 days after symptom onset.17
5.2.2. Urgent CABG Surgery
Recommendation for Urgent CABG Surgery
Referenced studies that support recommendation are summarized in
the Evidence Table.
COR
LOE
Recommendation
2a
B-NR
1. In patients with STEMI in whom PCI is not feasible
or successful, with a large area of myocardium at
risk, emergency or urgent CABG surgery can be
effective to improve clinical outcomes.*1,2
*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.”3
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Synopsis
Trials that evaluated the efficacy and safety of CABG
surgery in STEMI are limited.4 When PCI is not possible
for anatomic reasons or in the presence of complex disease, CABG surgery can be performed as the primary
reperfusion strategy. After successful reperfusion of the
infarct-related artery, CABG surgery can also be important when managing patients with more extensive noninfarct-related artery disease (Section 7.4.1, “Management
of Multivessel CAD in STEMI”). The appropriate timing
of CABG surgery in patients with STEMI should be determined on an individual basis, taking into consideration
the hemodynamic stability of the patient, the presence of
ongoing ischemia, and extent of myocardium at risk. After failed PPCI, emergency CABG surgery is not recommended in the absence of a large area of myocardium at
risk or if surgical targets are poor and if surgery may be
associated with an increased risk of death and adverse
cardiovascular outcomes compared with nonsurgical
management.5 For recommendations regarding CABG
surgery in patients presenting with cardiogenic shock or
mechanical complications, please refer to Section 8.1,
“Revascularization in ACS With Cardiogenic Shock” and
Section 9.1, “Mechanical Complications.”
Recommendation-Specific Supportive Text
1. No RCTs have been done that compare PPCI with
surgical revascularization in the setting of STEMI.
For patients with STEMI who are hemodynamically
stable with anatomy of the infarct-related artery that
is not amenable to PPCI, or if PPCI is unsuccessful,
CABG surgery can be useful if there is a large area
of myocardium at risk. In such patients, particularly
in the presence of ongoing ischemia or if a large
area of myocardium is at risk, CABG surgery may be
effectively performed as a primary reperfusion strategy or after PPCI.1,2 Despite an increase in the acuity of presentation and the burden of comorbidities,
the in-hospital mortality rate after CABG surgery in
patients with STEMI continues to decrease.1,4
5.3. Reperfusion at Non–PCI-Capable Hospitals
Recommendations for Reperfusion at Non–PCI-Capable Hospitals
Referenced studies that support recommendations are summarized
in the Evidence Table.
COR
1
1
LOE
Recommendations
A
1. In patients with STEMI and an estimated time
from FMC to device activation of ≤120 minutes
or those with a contraindication to fibrinolytic
therapy, transfer to a PCI-capable hospital for
PPCI is recommended to reduce MACE.1–3
A
2. In patients with STEMI and symptom onset of
<12 hours and anticipated delay to PPCI >120
minutes from FMC, fibrinolytic therapy should
be administered in patients without contraindication to reduce MACE.4–10
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2025 Acute Coronary Syndromes Guideline
COR
2a
3: Harm
LOE
Recommendations
B-NR
3. In patients with STEMI and symptom onset of
12 to 24 hours, transfer to a PCI-capable
hospital for PPCI is reasonable to reduce
infarct size and MACE.11,12
B-R
4. In patients with only ST-segment depression, except when true posterior STEMI is
suspected, fibrinolytic therapy should not be
administered due to risk of hemorrhagic stroke
and major noncerebral bleeding.13
Synopsis
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A large proportion of patients globally live >1 hour driving
time to a PCI-capable hospital.14–17 At non–PCI-capable
hospitals, transfer for PPCI is recommended if device activation can be reasonably predicted to occur in <2 hours
from FMC. If this cannot be achieved and symptoms have
been present <12 hours, fibrinolytic therapy is recommended to reduce the risk of recurrent MACE. Patients
with STEMI who present to a non–PCI-capable facility
≥12 hours after onset of symptoms should be transferred to a PCI-capable facility when possible. However,
if the patient has associated hemodynamic instability or
a large infarct territory at risk, they are at very high risk
for morbidity and death, and in this situation where timely
PPCI is not possible, the benefits of fibrinolytic administration likely outweigh the benefit of prolonged transfer
for PPCI.
Recommendation-Specific Supportive Text
1. PPCI is recommended to reduce the risk of MACE
when FMC to PPCI can be achieved within 120
minutes. A patient who presents to a non–PCIcapable hospital with STEMI should be transferred
to a PCI-capable hospital when this intervention
can be accomplished within 120 minutes.1,2,18
System delays related to transfer are frequently
underestimated, and a case-by-case approach
should be calculated for each patient with STEMI
prior to transfer for PPCI.19–21
2. The use of fibrinolytic therapy in STEMI in the United
States is driven by patients who are unable to receive
timely PPCI (<120 minutes FMC to device activation). Numerous RCTs and meta-analyses have
demonstrated superiority to PPCI over fibrinolytic
therapy. However, the benefits of PPCI versus fibrinolytic therapy diminish with increasing PCI-related
time delay such that after 120 minutes, the benefits
are no longer as clear when compared with more
timely fibrinolytic therapy administration.19 In these
patients, when timely PPCI cannot be performed,
meta-analyses of RCTs and observational studies
show statistically similar morbidity and mortality
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rates for a pharmaco-invasive approach (eg, fibrinolytic therapy followed by PCI within 2 to 24 hours)
when a patient does not have timely access to
PPCI.4,5 The STREAM (Strategic Reperfusion Early
After Myocardial Infarction) trial, which randomized
1892 early presenters (symptoms <3 hours) with
STEMI unable to receive PCI within 1 hour of FMC,
found that both a 30-day composite (eg, death,
shock, CHF, or reinfarction) and 1-year mortality
rates were similar for prehospital fibrinolysis versus
transfer for PPCI.10,22
3. Small studies suggest that PPCI continues to offer
clinical benefit in patients 12 to 24 hours after symptoms onset; therefore, transfer to a PCI-capable hospital is reasonable.11,12 Late presenters with STEMI
who have associated hemodynamic instability or
large infarct size are at very high risk for acute deterioration and long-term morbidity. In this situation,
fibrinolytic administration may outweigh potential
risks when timely PPCI is not possible. Fibrinolysis
in this setting should be followed by transfer to a
PCI-capable center as soon as feasible.
4. There is no benefit of fibrinolysis and there is
potential harm (eg, hemorrhagic stroke and major
noncerebral bleeding) in administering fibrinolytic
therapy to patients who present with symptoms
concerning for ACS without ST-segment elevation
or suspected true posterior STEMI.13
5.3.1. Timing and Choice of Agent for Fibrinolytic
Therapy
Synopsis
PPCI remains the reperfusion modality of choice when
it can be rapidly achieved in a patient with STEMI. In instances where this is not possible or cannot be achieved
in a timely manner, the benefits of coronary reperfusion
with fibrinolytic therapy in patients with STEMI are well
established, with a time-dependent reduction in both
mortality and morbidity rates during the initial 12 hours
after symptom onset, especially in those who present early after symptom onset with low bleeding risk and large
anterior infarctions.1–7 The benefit of fibrinolytic therapy
in patients who present >12 hours after symptom onset has not been established,8–10 although consideration
should be given to administering a fibrinolytic agent in
symptomatic patients presenting >12 hours after symptom onset of STEMI with a large area of myocardium
at risk or hemodynamic instability, if PCI is unavailable.
Fibrin-specific fibrinolytic therapies are preferred over
non–fibrin-specific agents due to superior patency rates
and less immunogenicity (Table 13).11–16 Tenecteplase is
a genetically engineered version of alteplase with higher
specificity for fibrin. In a large randomized trial of patients
with AMI, tenecteplase and alteplase were equivalent
for 30-day mortality rates, but tenecteplase was associated with reduced noncerebral bleeding.17 Reteplase (reTBD TBD, 2025
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CLINICAL STATEMENTS
AND GUIDELINES
Table 13. Fibrin-Specific Fibrinolytic Agents for STEMI
Table 14. Absolute and Relative Contraindications for Fibrinolytic Therapy in STEMI*
Fibrinolytic Agent
Dose
Tenecteplase (TNK-tPA)
Single IV weight-based bolus*
Absolute Contraindications
Reteplase (rPA)
Two 10-unit IV boluses given 30 min apart
(administered over 2 min)
Any prior ICH
Alteplase (tPA)
90-min weight-based infusion†
Known malignant intracranial neoplasm (primary or metastatic)
Streptokinase is no longer available in the United States.
*30 mg for weight <60 kg; 35 mg for 60-69 kg; 40 mg for 70-79 kg; 45 mg
for 80-89 kg; and 50 mg for ≥90 kg.
†Adults ≥67 kg: 100-mg total dosage administered as a 15-mg IV bolus, followed by 50-mg IV infused over 30 min, and then 35-mg IV infused over the
next 60 min. Adults <67 kg: 15-mg IV bolus, followed by 0.75 mg/kg IV (not to
exceed 50 mg) infused over 30 min, and then 0.5 mg/kg IV (not to exceed 35
mg) over the next 60 min.
rPA indicates reteplase plasminogen activator; TNK-tPA, tenecteplase tissuetype plasminogen activator; and tPA, tissue-type plasminogen activator.
Known structural cerebral vascular lesion (eg, arteriovenous malformation)
Ischemic stroke within 3 mo except acute ischemic stroke†
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding menses)
Significant closed-head or facial trauma within 3 mo
Intracranial or intraspinal surgery within 2 mo
Severe uncontrolled hypertension (unresponsive to therapy) (SBP >180
mm Hg or DBP >110 mm Hg)
Relative Contraindications
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combinant plasminogen activator) has not been shown
to improve survival compared with alteplase in patients
with MI, but its convenient bolus dosing allows for greater
ease of use.18 Adjunctive antiplatelet and/or anticoagulant therapies are indicated, regardless of the choice of
fibrinolytic agent (Sections 4.3.2., “Oral P2Y12 Inhibitors
During Hospitalization,” and 4.4, “Parenteral Anticoagulation”). Absolute and relative contraindications for fibrinolytic therapy are listed in Table 14.
Patients should be transferred to a PCI-capable
hospital after initiation of fibrinolytic therapy for routine
coronary angiography (Section 5.3.2., “Coronary Angiography and PCI After Fibrinolytic Therapy”). Signs of failed
reperfusion are discussed in Section 5.3.2.
5.3.2. Coronary Angiography and PCI After
Fibrinolytic Therapy
Recommendations for Coronary Angiography and PCI After Fibrinolytic
Therapy
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
LOE
Recommendations
1
A
1. In patients with STEMI, transfer to a
PCI-capable center immediately after
fibrinolytic therapy is recommended.1–5
B-R
2. In patients with STEMI with suspected
failed reperfusion after fibrinolytic therapy,
immediate angiography with rescue PCI is
recommended to reduce the risk of death or
recurrent MI.*6–9
B-R
3. In patients with STEMI treated with fibrinolytic therapy, early angiography between 2
and 24 hours with the intent to perform PCI
is recommended to reduce the rates of death
or MI.*1–5,10,11
1
1
*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery
Revascularization.”12
Synopsis
Failure of reperfusion and risk of reocclusion after successful fibrinolytic therapy are important limitations of
fibrinolytic therapy. For this reason, all patients receiving
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History of chronic, severe, poorly controlled hypertension
Significant hypertension on presentation (SBP >180 mm Hg or DBP >110
mm Hg)
History of prior ischemic stroke >3 mo
Dementia
Known intracranial pathology not covered in absolute contraindications
Traumatic or prolonged (>10 min) CPR
Major surgery (<3 wk)
Recent (within 2 to 4 wk) internal bleeding
Noncompressible vascular punctures
Pregnancy
Active peptic ulcer
Oral anticoagulant therapy
*Viewed as advisory for clinical decision-making and may not be all-inclusive
or definitive.
†Acute ischemic stroke within 4.5 h of onset.
CPR indicates cardiopulmonary resuscitation; DBP; diastolic blood pressure;
ICH, intracranial hemorrhage; SBP, systolic blood pressure; and STEMI, ST-segment elevation myocardial infarction.
fibrinolytic therapy should be transferred to a PCI-capable hospital to facilitate immediate or early catheterization depending on the clinical circumstances. Hospitals
should have transfer protocols in place to allow for a
seamless transfer to the PCI-capable facility as soon
as it is safe to do so. A detailed assessment of clinical
status is critical to determine the timing of angiography.
A lack of improvement in ischemic symptoms, persistent
ST-segment elevation (<50% resolution of ST-segment
elevation in the anterior leads or <70% in inferior leads
[measured either from the lead with maximal baseline ST
elevation or as the sum of ST-segment deviation across
leads]),13 or hemodynamic or electrical instability can indicate incomplete reperfusion by fibrinolytic therapy.14
When there are signs of failed reperfusion, patients
should undergo immediate coronary angiography and
rescue PCI. For the remaining patients, routine coronary
angiography within 2 to 24 hours after fibrinolytic therapy with coronary revascularization as needed is recommended.
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1. Numerous clinical trials have evaluated a strategy
of early coronary angiography with possible PCI
after fibrinolytic therapy. This strategy of immediate
transfer and angiography has been associated with
lower rates of recurrent ischemic events as compared with usual care.1–5 Regardless of the timing
of angiography, immediate transfer enables earlier
access to specialized centers, providing critical
care services and on-site catheterization laboratory
teams that can facilitate clinical assessments to
determine the likelihood of reperfusion and enable
earlier angiography for the unstable patient.
2. Rescue PCI is associated with improved outcomes
in patients with clinical signs of failed reperfusion after fibrinolytic therapy. Several trials have
demonstrated a trend toward lower mortality and
significantly lower rates of recurrent MI and HF
when rescue PCI is performed for failed fibrinolysis.6,7 The REACT (Rapid Early Action for Coronary
Treatment) trial6 enrolled 427 patients with failed
reperfusion at 90 minutes after fibrinolysis to 1 of
3 treatment arms, including rescue PCI, conservative care, or repeat fibrinolytic therapy. Rescue PCI
significantly reduced the composite primary endpoint of death, reinfarction, stroke, or severe HF at
6 months compared with either conservative care
or repeat fibrinolytic therapy. Meta-analyses also
support lower rates of death or reinfarction when
rescue PCI is performed in this setting.8,9 Minor
and major bleeding and rates of stroke were significantly higher with rescue PCI.6–8 These studies
were performed in the era of femoral artery access,
with fewer options for antiplatelet and anticoagulant therapy. The use of radial artery access15 and
the elimination of the routine use of glycoprotein
IIb/IIIa inhibitors has reduced bleeding. For this
reason, the balance of benefit from rescue PCI outweighs the risks for most patients with evidence of
failed reperfusion after fibrinolysis.
3. Routine early angiography with the intent to perform
PCI after fibrinolysis reduces MACE in comparison
to usual care (delayed coronary angiography and/
or an ischemia-guided strategy of revascularization).1–5,11,16 In these studies, >80% of patients
who were transferred underwent PCI to treat a significant residual stenosis or suboptimal flow of the
infarct-related artery. Meta-analyses of the RCTs
showed a reduction in the combined endpoint of
death or reinfarction with an early invasive approach
after fibrinolytic therapy.10,17,18 In a network metaanalysis evaluating clinical outcomes with different
modes of reperfusion for STEMI, a pharmaco-invasive strategy (defined as an interval between lysis
and PCI ≥2 hours) was associated with a 21%
reduction in the mortality rate when compared
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with a strategy of fibrinolysis alone.18 Furthermore,
contemporary registries have shown an association between a pharmaco-invasive approach and
improved outcomes compared with PPCI when
transfer times are long.19 The optimal timing of
angiography and PCI after fibrinolytic therapy has
not been clearly defined but a similar benefit in
ischemic endpoints is evident across the spectrum
of times included in the clinical trials.17,20 Although
earlier studies raised concerns for increased bleeding with very early catheterization (mean time, 2.2
hours),21 more contemporary data suggest similar
rates of bleeding even if cardiac catheterization is
performed very early after fibrinolytic therapy.17,20
6. NSTE-ACS: ROUTINE INVASIVE OR
SELECTIVE INVASIVE INITIAL APPROACH
6.1. Rationale and Timing for a Routine Invasive
or Selective Invasive Approach
Recommendations for Rationale and Timing for a Routine Invasive or
Selective Invasive Approach
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
LOE
Recommendations
Routine Invasive Versus Selective Invasive Strategy
1
1
A
1. In patients with NSTE-ACS who are at
intermediate or high risk of ischemic events and
are appropriate candidates for revascularization,
an invasive approach with the intent to proceed
with revascularization is recommended during
hospitalization to reduce MACE.*1–6
A
2. In patients with NSTE-ACS who are at low risk of
ischemic events, either a routine invasive or
selective invasive approach is recommended to
help identify those who may require
revascularization and to reduce MACE.1–4,7
Timing of Coronary Angiography for Those in Whom an Invasive
Approach Is Planned
1
C-LD
3. In patients with NSTE-ACS who have refractory
angina or hemodynamic or electrical instability, an
immediate invasive strategy with intent to perform
revascularization is indicated to reduce MACE.†8–11
2a
B-R
4. In patients with NSTE-ACS who are at high risk‡
of ischemic events, it is reasonable to choose an
early invasive strategy (within 24 hours) to reduce
MACE.†8,9,11,12
B-R
5. In patients with NSTE-ACS who are not at high
risk and are intended for an invasive strategy, it is
reasonable to perform angiography before
hospital discharge to reduce MACE.*8,11
2a
*Reproduced or
†modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.”7
‡Predictors of risk are outlined in Figure 8.
Synopsis
A routine invasive approach refers to a strategy of
performing coronary angiography with the intent to
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Recommendation-Specific Supportive Text
CLINICAL STATEMENTS
AND GUIDELINES
Rao et al
perform coronary revascularization by PCI or CABG (as
appropriate) in patients with NSTE-ACS. This approach
provides important prognostic information, including delineating the extent and severity of CAD. Several RCTs
have demonstrated that a routine invasive approach
in patients with NSTE-ACS reduces the risk of MACE
when compared with a selective invasive approach.1–3
Notably, these strategy trials were conducted in an era
prior to the availability of hs-cTn assays, routine use
of radial approach for coronary angiography, newer
generation drug-eluting stents, and contemporary evidence-based antiplatelet therapies. Patients who are
at prohibitively high risk from angiography or who have
known coronary anatomy or preferences that preclude
revascularization (PCI or CABG) may be managed noninvasively.13 In addition, some low-risk patients, particularly those who have normal cardiac biomarkers and
in whom a diagnosis of an ACS is questioned, should
be considered for a “selective invasive” approach that
includes further noninvasive risk stratification prior to
consideration of coronary angiography, because they
derive less benefit from a routine invasive approach.4,7,13
These low-risk patients should still undergo noninvasive stress testing or coronary CT angiography prior to
2025 Acute Coronary Syndromes Guideline
hospital discharge. Patients with higher risk findings
on noninvasive testing or who have recurrent ischemic
symptoms should be referred for invasive coronary angiography prior to hospital discharge in the absence of
contraindication (Figure 7).
Recommendation-Specific Supportive Text
1. In patients with NSTE-ACS, a routine invasive
approach improves clinical outcomes, including
lower rates of recurrent MI and recurrent ischemia, compared with a selective invasive approach
that involves further noninvasive risk stratification
prior to consideration of angiography.1–3 In a collaborative meta-analysis of RCTs, a routine invasive approach reduced death or MI by 18% (OR,
0.82 [95% CI, 0.72-0.93]), including a 25% reduction in MI (OR, 0.75 [95% CI, 0.65-0.88]) when
compared with a selective invasive approach.5 The
benefit was more apparent in higher risk patients
with elevated biomarkers.4 The studies that established the benefit of a routine invasive approach
were conducted in the late 1990s and early
2000s, and it is unknown whether contemporary
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Figure 7. Selection of a Routine Invasive Versus Selected Invasive Strategy in Patients With NSTE-ACS.
Colors correspond to Class of Recommendation in Table 2. *AHA Scientific Statement on MINOCA.17 CABG indicates coronary artery bypass
grafting; CCTA, cardiac CT angiography; MINOCA, myocardial infarction with nonobstructive coronary artery disease; NSTE-ACS, non–STsegment elevation acute coronary syndromes; and PCI, percutaneous coronary intervention.
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Rao et al
Table 15. Relative Contraindications for a Routine Invasive
Approach in ACS
High risk for bleeding on DAPT
Severe thrombocytopenia (platelet count <50 × 109/L)
Advanced kidney disease (not on dialysis)
Acute renal failure
Limited (<1-2 y) life expectancy
Advanced dementia
Known coronary anatomy that precludes PCI and/or CABG surgery
Patient preference
ACS indicates acute coronary syndromes; CABG, coronary artery bypass grafting; DAPT, dual antiplatelet therapy; and PCI, percutaneous coronary intervention.
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
3. Patients with NSTE-ACS who are unstable (eg,
refractory or recurrent angina [despite optimal
medical therapy, hemodynamic or electrical instability, acute pulmonary edema or HF, worsening mitral
regurgitation]) have been largely excluded from
RCTs. Despite a relative paucity of clinical trial data,
these patients are at heightened risk of adverse
outcomes, and an immediate invasive strategy (<2
hours from hospital admission) with intention to
perform revascularization is recommended.8,15 If
patients with ACS and unstable features are at a
non–PCI-capable hospital, they should be immediately transferred to a PCI-capable facility with a
goal of immediate angiography. Clinical features
that support immediate coronary angiography with
intent to revascularize are listed in Figure 8.
4. For patients with NSTE-ACS for whom the decision has been made to proceed with coronary
angiography, the benefit of an early invasive versus a delayed invasive approach is unclear.8,9,11,12
In the TIMACS (Timing of Intervention in Acute
Coronary Syndromes) trial,11 patients were enrolled
within 24 hours of symptoms and randomized to
early angiography within 24 hours versus delayed
angiography ≥36 hours from time of randomization.
In the VERDICT (Very Early vs Deferred Invasive
Evaluation Using Computerized Tomography)
trial,12 patients were randomized to early angiography within 12 hours versus delayed between 48
to 72 hours from time of diagnosis. Both studies
reported no significant difference in MACE between
an earlier versus delayed invasive approach in the
overall study populations, but there was signal
toward a reduction in MACE with an earlier invasive
approach in the higher risk patients with a GRACE
risk score >140.11,12 In a meta-analysis of RCTs
that compared an early versus delayed approach, a
mortality benefit was not seen with earlier angiography. However, factors that favored an earlier invasive approach included a GRACE risk score >140,
diabetes, age >75 years, and elevated cardiac biomarkers (although formal tests for interaction were
not significant).8 Although not evaluated in RCTs, a
continuing steep rise in cardiac biomarkers, likely
due to ongoing ischemia and myonecrosis despite
optimized medical therapy, may also favor earlier
coronary angiography.
5. In intermediate- or low-risk patients for whom
angiography is planned in NSTE-ACS, timing does
not appear to be critical, and a delayed invasive
strategy within 48 to 72 hours does not appear to
increase future risk of MACE.8,10–12,15 Randomized
trial data have not demonstrated an overall significant difference in death or MI between an earlier
versus delayed invasive approach in nonselected
patients with NSTEMI.8,11,12,16
TBD TBD, 2025
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therapies and advances in interventional methods
would yield different results. Similarly, elevated
cardiac biomarkers (CK-MB and older generation troponin assays) identify those who benefit
more from a routine invasive strategy; however,
it remains unknown whether hs-cTn assays that
detect smaller degrees of myonecrosis are as useful for identifying those who benefit from routine
coronary angiography. Although women are less
likely to have obstructive coronary disease at angiography, they derive as much benefit from a routine invasive approach in the presence of similar
risk predictors.4 The GRACE 2.0 risk calculator
and TIMI Risk Score for unstable angina/NSTEMI
may help identify patients at increased risk of
MACE who benefit more from a routine invasive
approach (Table 5).1 Relative contraindications to
coronary angiography that merit further consideration of the relative risks and benefits of a routine
invasive approach are outlined in Table 15.
2. Although some trials have demonstrated a reduction in MACE with a routine invasive approach in
NSTE-ACS,1–3 others have not demonstrated a
significant benefit when compared with a selective
approach that involves further risk stratification.4,7
Although a pooled analysis of 3 randomized trials suggested that the benefit of a routine invasive
approach was independent of baseline risk,6 other
meta-analyses across studies have suggested
that lower risk patients may derive less benefit.4,5,14 In addition, some low-risk patients, particularly those who have normal cardiac biomarkers
in whom a diagnosis of an ACS is suspect, may
have improved outcomes with a selective invasive
approach.4,5 These patients should preferentially
undergo noninvasive stress testing or coronary
CT angiography prior to hospital discharge to help
determine the need for coronary angiography;
however, patients with suspected ongoing ischemic symptoms should be considered for coronary
angiography.
2025 Acute Coronary Syndromes Guideline
2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
Rao et al
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Figure 8. Selection and Timing of an Invasive Strategy in NSTE-ACS.
Figure 8 summarizes the recommendations in the 2025 ACS Guideline for a routine or selective invasive approach in NSTE-ACS. It is not meant
to encompass every patient scenario or situation, and clinicians are encouraged to use a Heart Team approach when care decisions are unclear
and to see the accompanying supportive text for each recommendation. Colors correspond to Class of Recommendation in Table 2. GRACE
indicates Global Registry of Acute Coronary Events; HF, heart failure; NSTE-ACS, non–ST-segment elevation acute coronary syndromes; Tn,
troponin; TIMI, Thrombolysis in Myocardial Infarction; VF, ventricular fibrillation; and VT, ventricular tachycardia. Adapted with permission from
Lawton et al.18 Copyright 2022 American Heart Association, Inc., and American College of Cardiology Foundation.
7. CATHETERIZATION LABORATORY
CONSIDERATIONS IN ACS
7.1. Vascular Access Approach for PCI
Recommendation for Vascular Access Approach for PCI
Referenced studies that support recommendation are summarized in
the Evidence Table.
COR
1
LOE
Recommendation
A
1. In patients with ACS undergoing PCI, a radial
approach is preferred to a femoral approach to
reduce bleeding, vascular complications, and
death.*1–6
*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.”7
Synopsis
The radial artery has become the preferred vascular access site for patients undergoing cardiac catheterization
and PCI.8,9 Transradial access is associated with lower
mortality, bleeding, and vascular complications in patients treated for ACS.5 In addition, patients prefer radial
access because it allows earlier ambulation and causes
less discomfort than femoral access.9 A caveat is most
trials comparing radial versus femoral access had very
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low crossover rates because they required operators with
expertise in radial access.3 The choice of radial access has
to be weighed against the possibility that the radial artery
could be used as a bypass conduit for CABG surgery.10
In sites where surgeons routinely utilize the radial artery
as a bypass conduit, consideration should be given on
the choice of vascular access and future use of radial
artery for the cardiovascular surgical team. Although the
radial artery is the most widely studied wrist access site,
the use of alternative sites in the upper extremity, including the ulnar and distal radial arteries have yielded similar
outcomes.11,12 Transfemoral access, preferably with the
use of ultrasound guidance, should be considered in patients in whom temporary MCS is planned and is the default alternative access site among patients in whom the
radial artery cannot be used due to clinical, anatomical,
or technical reasons.13
Recommendation-Specific Supportive Text
1. RCTs have consistently demonstrated the benefit of radial access in comparison with femoral
access among patients treated for ACS. A metaanalysis using individual patient data from 7 highquality RCTs (48.6% with NSTE-ACS; 46.2% with
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2025 Acute Coronary Syndromes Guideline
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7.2. Use of Aspiration Thrombectomy
Recommendation for Use of Aspiration Thrombectomy
Referenced studies that support recommendation are summarized in
the Evidence Table.
COR
LOE
Recommendation
3: No
benefit
A
1. Among patients with STEMI undergoing PPCI,
manual aspiration thrombectomy should not be
performed routinely prior to PCI given lack of
clinical benefit.*1–4
*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.”5
Synopsis
Despite restoration of coronary patency, suboptimal myocardial perfusion resulting from distal embolization or microvascular obstruction is frequent and is associated with
larger infarct size, impairment of LV function, and excess
mortality rates.6,7 Removing coronary artery thrombus prior to balloon angioplasty, stent deployment, or both is an
intuitive adjunct to PPCI that may yield putative clinical
benefits. Routine manual thrombus aspiration performed
via low profile catheters improved electrocardiographic
and angiographic markers of myocardial perfusion in
several clinical studies8,9 and reduced adverse events in
a single-center trial.10,11 However, subsequent trials of
manual aspiration thrombectomy have not demonstrated
a clinical benefit.1,2,4,12,13 Similarly, results from a pooled
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
analysis showed that mechanical thrombectomy during
STEMI was not superior to conventional PCI alone.
Recommendation-Specific Supportive Text
1. Results from several RCTs have shown that routine
manual aspiration thrombectomy prior to PCI does
not reduce MI size or improve clinical outcomes as
compared with PCI alone.1,2,4,12,13 In a patient-level,
pooled analysis comprising 3 RCTs, aspiration
thrombectomy did not reduce the primary endpoint
of cardiovascular death at 30 days among patients
with STEMI undergoing PPCI (n=18 306).3
Similarly, aspiration thrombectomy did not lower
risks for recurrent MI, target vessel revascularization, stent thrombosis, or HF at 30 days or 1 year.
With respect to safety, the incidence of stroke or
transient ischemic attack at 30 days and 1 year
was numerically higher, albeit not statistically significant, among patients who underwent aspiration
thrombectomy. Reductions in cardiovascular death
were lower while risks for stroke or transient ischemic attack were higher among those with a large
thrombus burden treated with aspiration thrombectomy. Dedicated studies are warranted to evaluate
the role of selective aspiration thrombectomy in
those high-risk patients most likely to benefit from
thrombus removal prior to PCI. Manual aspiration
thrombectomy may be performed as a bailout procedure to remove thrombus that persists after balloon angioplasty or stent deployment, particularly
with concomitant no-reflow. Estimates from RCT
cohorts indicate that 4% to 7% of patients with
STEMI undergoing PPCI will require bailout aspiration thrombectomy.1,2,10
7.3. Use of Intracoronary Imaging
Recommendation for Use of Intracoronary Imaging
Referenced studies that support recommendation are summarized in
the Evidence Table.
COR
1
LOE
Recommendation
A
1. In patients with ACS undergoing coronary stent
implantation in left main artery or in complex
lesions, intracoronary imaging with intravascular
ultrasound (IVUS) or optical coherence tomography (OCT) is recommended for procedural
guidance to reduce ischemic events.*1–11
*Adapted from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.”12
Synopsis
Intracoronary imaging serves as a valuable tool for guiding the placement of coronary stents, particularly in cases
involving the left main artery or complex lesions, resulting
in greater stent expansion, less stent malapposition, and
fewer coronary dissections.1,2,4,13 IVUS provides a comTBD TBD, 2025
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STEMI) demonstrated that radial access was independently associated with a significant 24% and
51% relative risk reduction of all-cause death and
major bleeding, respectively, when compared with
femoral access.3 The magnitude of the mortality benefit was greater among patients with lower
baseline hemoglobin levels. The benefit of radial
access toward reducing bleeding was driven by
a significant reduction in access-site bleeding.
Vascular complications were significantly reduced
by 62%. The MATRIX trial6 demonstrated a significantly lower rate of the coprimary endpoints of
MACE and net adverse clinical events (composites
of death, MI, and stroke at 30 days, and MACE plus
non-CABG major bleeding) among patients with
ACS randomized to the transradial approach compared with the transfemoral approach. This is consistent with prior meta-analyses that have reported
lower mortality and bleeding with radial access in
patients with ACS.4,14 The SAFARI-STEMI (Safety
and Efficacy of Femoral Access versus Radial for
Primary Percutaneous Intervention in ST-Elevation
Myocardial Infarction) trial showed no difference in
30-day mortality rates between radial and femoral access; however, the trial stopped early and
therefore was underpowered to detect a mortality
benefit.15
CLINICAL STATEMENTS
AND GUIDELINES
Rao et al
prehensive view of the vessel wall, allowing for the evaluation of plaque burden, calcification extent, lesion length,
and external elastic lamina diameter before stent placement. It also facilitates the assessment of minimum stent
area, malapposition, underexpansion, tissue protrusion,
edge disease, and edge dissection after stent deployment.14 OCT utilizes infrared light to produce high-resolution images of the vessel wall, offering specific advantages in assessing calcium thickness, lipid presence,
thrombus formation, fibroatheroma, and plaque rupture,
which is particularly helpful in patients with ACS. It is also
useful for examining stent strut neointimal thickness, apposition, and edge dissections. However, it has limitations regarding imaging depth and requires the injection
of contrast to clear blood, limiting its utility in cases of ostial left main disease. Both IVUS and OCT play essential
roles in evaluating the necessity for lesion preparation,
choosing the appropriate stent size, reducing the likelihood of geographical errors, confirming proper stent expansion, identifying complications, and determining the
underlying reasons for stent failure.14,15
2025 Acute Coronary Syndromes Guideline
were also significantly lower with OCT-guided PCI
compared with angiography-guided PCI. A minimum
stent area of <4.5 to 5.0 mm2 by OCT is considered
to be an independent predictor of MACE.16,17 Two
large network meta-analyses showed that, in aggregate, intracoronary imaging guidance (with either
IVUS or OCT) for PCI decreases cardiac death, target vessel MI, target lesion revascularization, and
stent thrombosis.11,18
7.4. Management of Multivessel CAD in ACS
7.4.1. Management of Multivessel CAD in STEMI
Recommendations for Management of Multivessel CAD in STEMI
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
LOE
Recommendations
A
1. In selected, hemodynamically stable patients with
STEMI and multivessel disease (MVD), after
successful PCI of the infarct-related artery, PCI of
significantly stenosed* noninfarct-related
arteries is recommended to reduce the risk of
death or MI and improve angina-related quality of
life (QOL).†1–9
C-EO
2. In appropriate patients with STEMI and complex
MVD, after successful PCI of the infarct-related
artery, elective CABG surgery for significantly
stenosed noninfarct-related arteries involving the
left anterior descending artery or left main
disease is reasonable to reduce the risk of
cardiovascular events.†
B-R
3. In selected hemodynamically stable patients
with STEMI and low-complexity MVD (those not
intended for CABG surgery), multivessel PCI
of significantly stenosed noninfarct-related
arteries at the time of PPCI may be preferred over
a staged approach to reduce the risk of
cardiovascular events.10–12
B-R
4. In patients with STEMI complicated by cardiogenic
shock, routine PCI of a noninfarct-related artery
at the time of PPCI should not be performed
because of the higher risk of death or renal
failure.*13–15
1
Recommendation-Specific Supportive Text
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1. Randomized trials including patients with ACS
have shown that intracoronary imaging guidance
is associated with lower risk of target vessel failure
(cardiac death, target vessel MI, or ischemia-driven
target vessel revascularization) in patients undergoing PCI.1–4 The advantages of intracoronary imaging are sustained over time and can be extended
to less complex lesions.5 Renovate-Complex PCI
(Randomized Controlled Trial of Intravascular
Imaging Guidance versus Angiography-Guidance
on Clinical Outcomes after Complex Percutaneous
Coronary Intervention) demonstrated a significant
reduction in target vessel failure with intracoronary guidance (IVUS or OCT) versus angiographic
guidance after a median follow-up of 2.1 years.1
The OCTOBER (Optical Coherence Tomography
Optimized Bifurcation Event Reduction) trial showed
a significant reduction in target vessel failure at 2
years with OCT versus angiographic guidance in
bifurcation lesions, including left main bifurcations.4
Randomized trials directly comparing OCT versus
IVUS have demonstrated that OCT is noninferior to
IVUS for PCI-guidance.6–8,10 However, the ILUMIEN
IV: Optimal PCI (OCT Guided Coronary Stent
Implantation Compared with Angiography) trial, the
largest trial testing the strategy of imaging guidance
with OCT, did not reveal a difference in target vessel
failure with OCT in high-risk patients or patients with
high-risk lesions; however, the coprimary endpoint of
minimal stent area was significantly larger with OCT
guidance compared with angiography guidance.2
The rates of definite or probable stent thrombosis
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2a
2b
3: Harm
*Significantly stenosed refers to lesions that are severely diseased as defined
by the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization”
as a visually estimated diameter stenosis severity of ≥70% for non–left main
disease and ≥50% for left main disease.16
†Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.”16
Synopsis
Several randomized trials of hemodynamically stable patients with STEMI have demonstrated that a strategy of
multivessel PCI of significantly stenosed nonculprit vessels is safe and reduces risk of MACE when compared
with PCI of the infarct-related artery alone.1–8 These trials
enrolled a select group of patients with anatomy suitable
for PCI and without clinical factors precluding further invasive therapies. Recent studies suggest a lower risk of
MACE (predominantly driven by a lower rate of recurrent ischemia and recurrent MI) when multivessel stentCirculation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
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Recommendation-Specific Supportive Text
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1. Over the past decade, numerous trials have reported
a significant reduction in MACE with complete revascularization.1,2,4–8 These studies have demonstrated
benefits to complete revascularization either at the
time of PPCI2,5–8 or as a staged procedure.1,2,4,6 The
PRAMI (Preventive Angioplasty in Acute Myocardial
Infarction) trial,8 one of the earliest trials of multivessel PCI, randomized 465 patients with STEMI
and MVD to a strategy of complete revascularization versus culprit artery only revascularization. The
trial was stopped early due to a significant reduction
in the primary composite endpoint (cardiovascular
death, nonfatal MI, or refractory angina) with complete revascularization, with significant reductions
in nonfatal MI and refractory angina and a trend
in reduction in the rates of cardiovascular death.
The COMPLETE (Complete versus Culprit-Only
Revascularization Strategies to Treat Multivessel
Disease after Early PCI for STEMI) trial1 randomized
4041 patients with STEMI and significant MVD to
a strategy of staged PCI of the non–infarct-related
artery (performed up to 45 days post MI) or culprit
vessel–only revascularization with PCI reserved for
patients with refractory symptoms. At a median
follow-up of 3 years, multivessel PCI reduced cardiovascular death or MI and cardiovascular death,
MI, or ischemia-driven revascularization. This benefit
was consistent across all subgroups. Angina-related
QOL was also significantly improved with multivessel PCI, with a greater proportion of patients in the
complete revascularization arm who were anginafree in long-term follow-up.9 In a meta-analysis, complete revascularization reduced cardiovascular death
in patients with STEMI.19 The benefits of complete
revascularization with multivessel PCI should not be
extrapolated to patients with disease more suited to
CABG surgery, because they were excluded from
these trials.
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
2. The trials examining the benefit of multivessel
PCI in patients with STEMI and MVD excluded
patients intended for CABG surgery. Furthermore,
few patients with complex disease, such as chronic
total occlusions or involvement of the left main
artery, were included in these trials. For this reason, the benefits of a strategy of multivessel PCI
cannot be extrapolated to patients with more complex noninfarct-related artery disease. In patients
with CCD and complex CAD, including complex
left main disease, or in patients with diabetes who
have MVD involving the left anterior descending
artery, CABG surgery is associated with improved
event-free survival when compared with PCI.20–24
As such, a similar benefit of CABG over PCI might
be expected for patients with STEMI and complex
non–infarct-related artery disease involving the left
main or left anterior descending artery or in patients
with diabetes and MVD involving the left anterior
descending artery, who are stable and remote from
their acute infarct, although the optimal timing of
CABG is unclear in this setting and needs to take
into account increased bleeding risk from DAPT.
3. Performing multivessel PCI at the time of PPCI
offers the convenience of a single procedure,
allowing for faster recovery, without the risk of
repeated arterial access, or the potential for
recurrent ischemia before the staged PCI. The
BIOVASC (Direct Complete Versus Staged
Complete Revascularization in Patients Presenting
With Acute Coronary Syndromes and Multivessel
Disease) trial10 randomized 1525 patients with
ACS (∼40% with STEMI) and MVD to a strategy
of a single setting immediate multivessel PCI or
staged multivessel PCI. At 1 year, immediate multivessel PCI was noninferior to staged multivessel PCI for the primary endpoint all-cause death,
MI, unplanned ischemia-driven revascularization,
or cerebrovascular events. When compared with
staged PCI, a single procedure multivessel PCI was
associated with lower rates of recurrent MI and
lower rates of unplanned ischemia-driven revascularization. The MULTISTARS AMI (Multivessel
Immediate Versus Staged Revascularization in
Acute Myocardial Infarction) study11 compared a
strategy of a single procedure multivessel PCI with
staged multivessel PCI in 840 patients with STEMI
and MVD. Immediate multivessel PCI was noninferior and superior to staged multivessel PCI for
the primary endpoint of death, reinfarction, stroke,
unplanned ischemia-driven revascularization, or
hospitalization for HF at 1 year. This was largely
driven by a lower rate of recurrent ischemia and
recurrent infarction in the immediate group. In a
network meta-analysis comparing all strategies for
managing the non–infarct-related artery, a single
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ing occurs as a single procedure as opposed to when
staged.10–12 The decision to proceed with multivessel
stenting and the timing of the procedure should take into
account the patient’s clinical and hemodynamic status,
the duration and complexity of the infarct-related artery
PCI, the complexity of disease in the noninfarct-related
artery, the amount of myocardium in jeopardy, and the
presence of comorbidities that might favor a conservative
approach to care. Few studies of multivessel PCI have
directly compared the efficacy of a physiologic-guided
PCI versus an angiographic-guided PCI approach.17,18 A
meta-analysis across trials did not suggest any differential benefit for complete revascularization based on
whether the approach was guided by fractional flow reserve (FFR) or angiography alone.3
2025 Acute Coronary Syndromes Guideline
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2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
procedure approach for immediate multivessel
PCI was preferred followed by staged multivessel
PCI.12 Patients ideally suited for immediate complete revascularization include those with uncomplicated PCI of the infarct-related artery and low
complexity noninfarct-related artery disease with
stable hemodynamics, normal LV filling pressures,
and normal renal function.
4. In patients with STEMI complicated by cardiogenic
shock and MVD, a strategy of multivessel PCI is
associated with worse outcomes.13–15 The CULPRITSHOCK (Culprit Lesion Only PCI versus Multivessel
PCI in Cardiogenic Shock) trial13 randomized 706
patients with AMI, approximately 60% with STEMI,
and cardiogenic shock to a strategy of complete
multivessel PCI or culprit vessel–only PCI. At 30
days and 1 year, the rates of death or need for renal
replacement therapy were significantly higher in the
group of patients randomized to multivessel PCI.13,14
Importantly, the CULPRIT-SHOCK trial only permitted
enrollment if there was an identifiable culprit lesion.
In situations where an unstable-appearing nonculprit
artery lesion was observed, or in those patients with
an uncertain culprit lesion, the decision to proceed
with multivessel PCI may be more nuanced.
7.4.2. Management of Multivessel CAD in
NSTE-ACS
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Recommendations for Management of Multivessel CAD in NSTE-ACS
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
LOE
Recommendations
1
C-EO
1. In patients with NSTE-ACS with MVD, the mode
of revascularization (CABG or multivessel PCI)
should be based on the disease complexity and
patient’s comorbidities.
Multivessel CAD and Candidates for PCI
1
2b
3: Harm
B-R
2. In stable patients with NSTE-ACS with MVD but
without left main stenosis who are not intended
for CABG surgery and undergoing culprit-lesion
PCI, PCI of significant nonculprit lesions (at the
time of the index procedure or as a staged
procedure) is recommended to reduce the risk of
MACE.1–6
B-R
3. In patients with NSTE-ACS in whom multivessel
PCI is being considered, physiological
assessment of a nonculprit stenosis may be
considered to guide revascularization decisions.7–9
B-R
4. In patients with NSTE-ACS complicated by
cardiogenic shock, routine PCI of a nonculprit
artery at the time of index procedure should not
be performed because of the higher risk of death
or kidney failure.*10,11
*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.”12
Synopsis
Multivessel coronary disease, defined as angiographically significant stenosis (≥50%) in ≥2 epicardial arteries, is present in up to 40% to 70% of patients with
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NSTE-ACS. Identification of the culprit artery in these
situations might be challenging.13 Several subsets of patients, including those with complex left main disease,
complex 3-vessel disease, and diabetes with left anterior descending artery involvement, might be appropriate for CABG surgery.12 A Heart Team approach is
recommended to consider CABG surgery versus multivessel PCI based on the complexity of CAD, technical feasibility, patient's surgical risk, and the potential
for rehabilitation after CABG surgery. Dedicated RCTs
comparing multivessel PCI versus culprit-only PCI exclusively among hemodynamically stable patients with
NSTE-ACS are lacking. A large subgroup analysis from
an RCT that included both patients with STEMI and
NSTE-ACS and several observational studies have suggested that multivessel PCI among selected patients not
intended for CABG reduces risk of MACE.1–4,6,15 Angiographic assessment might overestimate the severity of
a nonculprit lesion.16 In one study, routine integration of
physiological assessment of a nonculprit artery stenosis
in NSTE-ACS led to change in management (ie, from
revascularization to medical treatment only) in 38% of
the cases.17
Recommendation-Specific Supportive Text
1. Studies evaluating the benefit of multivessel PCI
among patients with NSTE-ACS and MVD
excluded patients planned for CABG. The potential benefit of multivessel PCI cannot be extrapolated to patients with complex CAD. Indeed,
certain subsets of patients might derive a survival
benefit from CABG, including those with diabetes
and disease involving the left anterior descending
artery, left main with high complexity, MVD with
complex or diffuse CAD, and those with severe
LV dysfunction (Table 16).18–21 Accordingly, a
Heart Team approach is recommended to consider CABG surgery versus multivessel PCI
based on the complexity of the CAD, technical
Table 16. Considerations for Choice of Coronary Revascularization Strategy for Patients With NSTE-ACS and MVD
In patients with NSTE-ACS and MVD, CABG surgery may be preferred
over multivessel PCI in any of the following situations:
Significant left main coronary stenosis with high-complexity CAD
Multivessel CAD with complex or diffuse CAD
Diabetes mellitus and MVD with the involvement of the LAD
Multivessel CAD or complex left main CAD with severe left ventricular
dysfunction
Adapted from the “2021 ACC/AHA/SCAI Coronary Revascularization Guideline.”12
CAD indicates coronary artery disease; CABG, coronary artery bypass grafting; LAD, left anterior descending artery; MVD, multivessel disease; NSTE-ACS,
non–ST-segment elevation acute coronary syndromes; and PCI, percutaneous
coronary intervention.
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Of note, the trial was prematurely terminated due
to slow recruitment and enrolled <50% of the
planned 1292 patients.9 In the FAMOUS-NSTEMI
(Fractional Flow Reserve Versus Angiographically
Guided Management to Optimise Outcomes in
Unstable Coronary Syndromes) trial, which randomized 350 patients with NSTE-ACS and MVD
to FFR-guided PCI (if FFR ≤0.80) or angiography-guided PCI (diameter stenosis of >30%),
FFR-guided PCI reduced the number of revascularization procedures at 1 year.8
4. In patients with NSTE-ACS complicated by cardiogenic shock and MVD, multivessel PCI at the
time of the index procedure is associated with
worse outcomes.10,11 The CULPRIT-SHOCK
(Culprit Lesion Only PCI versus Multivessel PCI in
Cardiogenic Shock) trial randomized 706 patients
with AMI and cardiogenic shock (approximately
40% with NSTE-ACS) to multivessel PCI at the
time of the index procedure or culprit-only PCI.
Multivessel PCI was associated with higher rates
of death or need for renal replacement therapy at
30 days and at 1 year.10,11 Notably, the CULPRIT
SHOCK trial enrolled only patients with an identifiable culprit lesion. When there is an unstableappearing nonculprit, or uncertain culprit, artery
lesion, the decision to proceed with multivessel
PCI will be based on the anatomic and clinical
circumstances.
8. CARDIOGENIC SHOCK MANAGEMENT
8.1. Revascularization in ACS With Cardiogenic
Shock
Recommendations for Revascularization in ACS With Cardiogenic
Shock
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
1
3: Harm
LOE
Recommendations
B-R
1. In patients with ACS and cardiogenic shock or
hemodynamic instability, emergency
revascularization of the culprit vessel by PCI or
with CABG is indicated to improve survival,
irrespective of time from symptom onset.1–4
B-R
2. In patients with ACS complicated by cardiogenic
shock, routine PCI of a noninfarct-related artery
at the time of PPCI should not be performed
because of the higher risk of death or renal
failure.*5–7
*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery
Revascularization.”8
Synopsis
In patients with STEMI and hemodynamic instability,
treatment delays to PPCI are associated with worse
survival.1 In patients with cardiogenic shock, PCI of
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feasibility, patient’s surgical risk, and the potential for rehabilitation after CABG surgery in these
situations. In patients who are deemed appropriate for CABG, surgery could be considered prior
to hospital discharge. Several observational studies have suggested that early CABG (performed
within 3 days of presentation) may be associated
with similar outcomes compared with delayed
CABG.22–24
2. The FIRE (Functional Assessment in Elderly MI
Patients With Multivessel Disease) trial enrolled
1445 elderly patients (median age, 80 years)
with multivessel disease (ie, nonculprit artery with
minimum vessel diameter >2.5 mm and angiography estimated stenosis 50% to 99%) and ACS
(∼65% with NSTE-ACS). Multivessel PCI reduced
the risk of MACE, as well as reduced all-cause
and cardiovascular mortality. The benefit was consistent between patients with NSTE-ACS versus
patients with STEMI.1 Several observational studies and a meta-analysis of observational studies
demonstrated that multivessel PCI is associated
with a lower incidence of long-term MACE.2,3,6
Few RCTs have evaluated the optimal timing of
a multivessel PCI approach. The SMILE (Single
Staged Versus Multistaged PCI in Multivessel
NSTEMI Patients) trial enrolled 584 patients and
demonstrated that multivessel PCI conducted in
a single procedure reduces risk of MACE at 1
year driven by a lower risk of revascularization.4
The BIOVASC trial randomized 1525 patients
with ACS (∼60% with NSTE-ACS) and showed
that multivessel PCI in a single procedure was
noninferior to staged PCI with respect to MACE
at 1 year and without evidence of an interaction
between patients with NSTE-ACS versus patients
with STEMI.5,25
3. In a secondary analysis including 328 patients with
NSTE-ACS and MVD from the FAME (Fractional
Flow Reserve Versus Angiography for Multivessel
Evaluation) trial that randomized patients to either
angiography-guided PCI (if diameter stenosis
≥50%) or FFR-guided PCI (if FFR ≤0.80), FFRguided PCI reduced the number of stents and the
incidence of MACE at 2 years.7 The FRAME-AMI
(Fractional Flow Reserve vs. Angiography-Guided
Strategy for Management of Non-Infarction
Related Artery Stenosis in Patients with Acute
Myocardial Infarction) trial enrolled 562 patients
with ACS and MVD (∼53% with NSTE-ACS)
and were randomized to FFR-guided PCI (if FFR
≤0.80) or angiography-guided PCI (diameter stenosis of >50%). FFR-guided PCI reduced the
number of stents and the risk of MACE at 3.5
years with no evidence of interaction between
patients with NSTE-ACS and patients with STEMI.
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the culprit vessel only is recommended.5,6 Emergency
CABG is recommended in those patients in whom PCI
is not feasible.2,9 Immediate revascularization with PCI
or CABG is also recommended in high-risk patients
with NSTEMI who are in cardiogenic shock.2–5 The use
of MCS devices in patients with cardiogenic shock is
covered in Section 8.2, “MCS in Patients With ACS and
cardiogenic shock.”
Recommendation-Specific Supportive Text
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1. In the SHOCK (Should We Emergently
Revascularize
Occluded
Coronaries
for
Cardiogenic Shock) trial,2 reported in 1999,
patients with AMI and cardiogenic shock were
randomized to medical therapy or emergency
revascularization. Among the patients randomized
to revascularization, 64% of patients were referred
for PCI and 36% for CABG. The median time from
randomization to revascularization was 0.9 hours
for PCI and 2.7 hours for CABG. Despite lack of
a significant difference in the primary endpoint of
mortality at 30 days, emergency revascularization
with either PCI or CABG reduced the mortality
rate at 6 months,2 and the mortality benefit was
maintained through 1 and 6 years.10,11 In an observational analysis from the FITT-STEMI (Feedback
Intervention and Treatment Times in ST-Elevation
Myocardial Infarction) trial, for every 10-minute
delay in PPCI after 60 minutes from FMC, there
were an additional 3 to 4 deaths per 100 with a
>80% mortality rate beyond 6 hours of delay from
FMC.1 Therefore, it is recommended that PPCI
should be performed in patients with STEMI and
cardiogenic shock as soon as possible, ideally
within 90 minutes, to reduce the mortality rate.1,2
Observational studies suggest that emergency
CABG remains a treatment option in patients
with cardiogenic shock who are not amenable
to primary reperfusion with PCI3,4 or when PCI is
unsuccessful.4,12
2. In patients with STEMI complicated by cardiogenic shock and MVD, a strategy of multivessel
PCI is associated with worse outcomes.5–7 The
CULPRIT-SHOCK trial5 randomized 706 patients
with AMI (approximately 60% with STEMI) and
cardiogenic shock to a strategy of complete
multivessel PCI or culprit-only PCI. At 30 days
and 1 year, the rates of death or need for renal
replacement therapy were significantly higher in
the group of patients randomized to multivessel
PCI.5,6 Importantly, the CULPRIT SHOCK trial
permitted enrollment only if there was an identifiable culprit lesion. In situations where there is
an unstable appearing nonculprit artery lesion,
or in those patients with an uncertain culprit, the
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decision to proceed with multivessel PCI may be
more nuanced.
8.2. MCS in Patients With ACS and Cardiogenic
Shock
Recommendations for MCS in Patients With ACS and Cardiogenic
Shock
Referenced studies that support recommendations are summarized
in the Evidence Table.
COR
LOE
Recommendations
B-R
1. In selected* patients with STEMI and severe or
refractory cardiogenic shock, insertion of a
microaxial intravascular flow pump is reasonable
to reduce death.1
B-NR
2. In patients with mechanical complication of ACS,
short-term MCS devices are reasonable for
hemodynamic stabilization as a bridge to
surgery.2–4
B-R
3. In patients with AMI and cardiogenic shock, the
routine use of intra-aortic balloon pump (IABP) or
venoarterial extracorporeal membrane
oxygenation (VA-ECMO) is not recommended
due to a lack of survival benefit.5–9
2a
2a
3: No
benefit
*See supportive text.
Synopsis
Cardiogenic shock is estimated to occur in approximately
10% of patients with STEMI and is associated with an
early mortality rate of 40% to 50%.10,11 Several types of
devices for temporary MCS are available and have been
studied in patients with cardiogenic shock with variable
efficacy and increased risk of vascular complications.
IABP counterpulsation improves coronary perfusion and
reduces cardiac afterload. It is relatively easy to use and
has a smaller insertion profile, which is associated with
lower rates of vascular access site complications when
compared with other MCS devices.12,13 Percutaneous microaxial flow pumps unload the LV by draining blood from
the LV and pumping it to the ascending aorta. They are
dependent on adequate right ventricular function to fill the
LV and require adequate oxygenation of blood. VA-ECMO
provides both blood flow and oxygenation but increases
afterload. Randomized trials of MCS devices remain challenging to conduct due to relative lack of equipoise on
the part of treating physicians, leading to selective patient
enrollment and limiting the generalizability of study results.
Although small studies of microaxial flow pumps did not
demonstrate clinical benefit for patients with AMI and
cardiogenic shock,14–16 a randomized trial at specialized
centers in Europe demonstrated a mortality benefit with
use of the microaxial flow pump in selected patients, albeit
with increased risk of complications, including limb ischemia and renal replacement therapy.1 Best practices for
insertion of all MCS devices, including the multimodality
use of fluoroscopy and ultrasound, should be utilized when
feasible for obtaining femoral access.17–19
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1. The DanGer-SHOCK (Danish-German Cardiogenic
Shock) trial enrolled patients with STEMI and
cardiogenic shock of <24 hours duration, defined
as hypotension (SBP <100 mm Hg or vasopressor support), end-organ hypoperfusion (arterial
lactate ≥2.5 mmol/L and/or SvO2 <55% with
a normal PaO2), and LVEF <45%. Patients who
were comatose (Glasgow Coma Scale score <8)
after out-of-hospital cardiac arrest and patients
with overt right ventricular failure were excluded.1
The study enrolled 360 patients at 14 specialized
centers in Europe and randomized them to use of
a microaxial flow pump or standard of care. Use
of a microaxial flow pump significantly reduced
the risk of all-cause mortality at 180 days by
26% (HR, 0.74 [95% CI, 0.55-0.99]; P =0.04;
absolute risk reduction, 12.7%; number needed
to treat =8) compared with standard of care. The
absolute risk reduction seen in this trial is similar
to the absolute risk reduction in 6-month mortality observed with emergency revascularization in
patients with AMI and LV failure in the SHOCK
(Should We Emergently Revascularize Occluded
Coronaries for Cardiogenic Shock) trial.1,20
However, given the increased risks of serious
complications like bleeding, limb ischemia, and
renal replacement therapy with the microaxial
flow pump seen in the DanGer Shock trial, the
COR is based on the balance between these
risks and the reduction in death. Additionally, the
timing of microaxial flow pump placement was
not dictated by the trial protocol; thus, the preferred timing of placement is unclear. Based on
these results, use of a microaxial flow pump is
reasonable to reduce mortality in patients with
STEMI and cardiogenic shock who have clinical
features consistent with the inclusion criteria of
the DanGer-SHOCK trial. In particular, patients
with STEMI who present with SCAI shock stages
C, D, or E, who are noncomatose and have adequate peripheral vasculature to accommodate
large-bore access are reasonable candidates for
the microaxial flow pump.
2. Although randomized trial data are lacking, MCS
devices can be considered as a bridge to surgery
for patients with mechanical complications of AMI
when adequate clinical stabilization is required
and may allow for further tissue stabilization at
the injured site. A systemic review of patients
treated with MCS as a bridge to surgical treatment
of ventricular septal rupture yielded 111 studies
(n=2440) with almost all patients receiving initial IABP support (n=2263).2 Of the 129 patients
who underwent additional MCS device placement
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(77.5% of whom were on VA-ECMO), the lowest in-hospital mortality was observed in those
treated with VA-ECMO (29.2%) when compared
with those treated with an IABP alone (52.0%).
However, 2 database analyses that were not
included in the systematic review demonstrated
higher in-hospital death with use of VA-ECMO
in patients with post-AMI mechanical complications.3,4 Evaluation of the ECLS (Extracorporeal
Life Support) Organizations Registry yielded 158
patients with post-AMI mechanical complications
who underwent VA-ECMO.3 Survival to hospital
discharge here was low at 37.3%, and complications related to VA-ECMO use occurred in 75.3%
of patients. Evaluation of the National Inpatient
Sample yielded 10 726 patients with postSTEMI mechanical complications, and the use
of VA-ECMO was associated with increased inhospital mortality (OR, 2.80 [95% CI, 1.92-4.04]),
while the use of an IABP was not associated with
lower mortality.4 Both data sources included use
of VA-ECMO at any time during the hospitalization
for post-AMI mechanical complications, including
use of VA-ECMO postsurgery, a cohort at highest
risk of in-hospital mortality.
3. The IABP-SHOCK II (Intraaortic Balloon Pump in
Cardiogenic Shock II) trial randomized patients
with AMI and severe or refractory cardiogenic
shock in whom early revascularization was planned
to IABP or no IABP.5 At 30 days and long-term
follow-up, no differences were observed in the primary outcome of all-cause death or the secondary
biomarker or measures of disease severity endpoints.6,7 VA-ECMO has not been shown to reduce
death compared with medical therapy alone in
patients with cardiogenic shock in the setting
of MI but increases major bleeding and vascular
complications.21 The ECMO-CS (Extracorporeal
Membrane Oxygenation in the Therapy of
Cardiogenic Shock) trial randomized patients
with rapidly deteriorating or severe cardiogenic
shock to immediate or no immediate VA-ECMO.8
At 30 days, no differences were observed in the
primary composite endpoint of all-cause death,
resuscitated cardiac arrest, and implementation of
another MCS device with results consistent in the
74 patients with cardiogenic shock related to MI
and in the as-treated analysis. The ECLS-SHOCK
(Extracorporeal Life Support in Infarct-Related
Cardiogenic Shock) trial randomized patients with
AMI and severe or refractory cardiogenic shock in
whom early revascularization was planned to early
ECLS or no ECLS.9 No differences were observed
in the primary outcome of the 30-day mortality
rate or secondary outcomes. Moderate or severe
bleeding and peripheral vascular complications
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requiring intervention were higher in the ECLS
versus no ECLS group. Overall, these studies do
not support routine use of IABP and VA-ECMO in
patients with AMI and cardiogenic shock.
9. ACS COMPLICATIONS
9.1. Mechanical Complications
Recommendations for Mechanical Complications
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
LOE
Recommendations
1
C-EO
1. Patients with a mechanical complication of
ACS should be managed in a facility with
cardiac surgical expertise.
2a
B-NR
2. In patients with a mechanical complication of
ACS, short-term MCS devices are reasonable
for hemodynamic stabilization as a bridge to
surgery.1–3
Synopsis
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Timely reperfusion therapy has reduced the incidence
of mechanical complications (ventricular septal rupture, mitral valve insufficiency due to papillary muscle
infarction or rupture, or free wall rupture) after AMI
(Figure 9).3,5 Although occasionally found incidentally,
mechanical complications commonly present with recurrent or refractory chest pain or a new murmur accompanied by disproportionate HF, cardiogenic shock,
or sudden cardiac death on clinical presentation within the first week after an AMI. Medical therapy alone
is associated with high risk of early death6,7; definitive surgical correction is frequently the treatment of
choice.8,9 Mortality rates with surgery are highest in
subjects with cardiogenic shock and in those requiring early emergency/urgent intervention after AMI.10,11
Observed mortality rates following delayed surgery
(>7 days) are lower but patient selection and survivor
bias contribute to this observation.12,13 The availability of temporary MCS devices has led to increasing
trends for delayed surgery due to concerns for the initial degree of extensive tissue destruction.14,15 Delayed
surgical intervention may enable hemodynamic stabilization, lead to recovery of end-organ injury, and promote infarct tissue healing and maturation that could
facilitate definitive repair. Percutaneous approaches
toward repair have been used in patients with prohibitive surgical risk or contraindications to surgery as a
primary or temporizing option in the setting of acute
mitral regurgitation and ventricular septal rupture and
remain an evolving area of investigation.16,17 Select patients with mechanical complications of ACS may be
considered for cardiac transplantation or durable left
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ventricular assist device as a primary or bailout treatment strategy to improve survival.18
Recommendation-Specific Supportive Text
1. No RCTs evaluate the role of transfer of patients
with mechanical complications after MI to dedicated centers with cardiac surgical expertise.
Although overall surgical mortality is approximately 40%, it remains the treatment strategy of
choice. Hemodynamic deterioration is unpredictable and can be precipitous in previously stable
subjects. Consequently, transfer to a Level 1
cardiac intensive care unit (CICU)19 with access
to various temporary MCS devices and multidisciplinary experienced teams of surgical, interventional, HF, and palliative care specialists is
recommended. Emerging data following the creation of shock teams supports the transfer of
hemodynamically unstable patients from community hospitals to centers with multidisciplinary
expertise.20,21 Although the exact timing remains
uncertain, early corrective surgery is the treatment of choice for mechanical complications of
MI.8,9,13 The risk of surgical correction is highest
when performed in the setting of cardiogenic
shock10,22,23 and appears lower when surgery is
delayed. The early hazard with surgery is attributed to patient acuity, end-organ injury, and lack
of tissue integrity to promote definitive and lasting repair. Selected subjects may be candidates
for either definitive or temporizing percutaneous
structural intervention as a bridge to definitive
surgical intervention.16,17,24 Given the complexity
of decision making, a Heart Team approach to
guide feasibility, timing, and nature of corrective
intervention as well as the need and selection
of MCS support is recommended as soon as a
mechanical complication is diagnosed.
2. No RCTs have evaluated the role of MCS in improving clinical outcomes in the setting of mechanical
complications. The choice of specific MCS should
be individualized and guided by patient characteristics, nature of the mechanical complication, and the
hemodynamic profile. In patients with ventricular
septal rupture, the use of an IABP has been shown
to reduce left-to-right shunting and improve hemodynamics in patients with and without shock.25
Favorable hemodynamic effects with IABP are
also noted with acute ischemic mitral regurgitation.
Various devices have been utilized when IABP fails
or if hemodynamic instability remains profound.1
The use of MCS devices has enhanced hemodynamic stabilization to allow the opportunity for consideration of delayed corrective strategy.14,15
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Figure 9. Clinical Characteristics of Mechanical Complications of Acute Myocardial Infarction.
Contained rupture is the preferred term for an entity sometimes referred to as pseudoaneurysm. HF indicates heart failure; LA, left atrium; LV, left
ventricle; and MR, mitral regurgitation. Modified with permission from Damluji et al.26 Copyright 2025 Devon Medical Art.
9.2. Electrical Complications and Prevention of
Sudden Cardiac Death After ACS
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Recommendations for Electrical Complications and Prevention of
Sudden Cardiac Death After ACS
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
LOE
Recommendations
Ventricular Arrhythmias
1. In patients post MI, implantable cardioverterdefibrillator (ICD) implantation is recommended
in selected patients with an LVEF ≤40% (Table
17) at least 40 days post MI and at least 90 days
postrevascularization to reduce death.*1–4
1
A
2a
C-EO
2. In patients post ACS, ICD implantation is
reasonable in patients with clinically relevant
ventricular arrhythmias >48 hours and within
40 days post MI to improve survival.*5,6
2b
B-R
3. In patients early after MI, usefulness of a
temporary wearable cardioverter-defibrillator
is uncertain in patients with an LVEF ≤35% to
improve survival.7
Bradyarrhythmias
1
B-NR
4. In patients presenting with an AMI with sustained
evidence of second-degree Mobitz type II
atrioventricular block, high-grade atrioventricular block, alternating bundle-branch block, or
third-degree atrioventricular block (persistent or
infranodal), permanent pacing is indicated.†8,9
*Adapted from the “2017 AHA/ACC/HRS Guideline for Management of
Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac
Death.”
†Adapted from the “2018 ACC/AHA/HRS Guideline on the Evaluation and
Management of Patients With Bradycardia and Cardiac Conduction Delay.”
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Synopsis
Electrical complications in patients with ACS may create challenges in clinical management due to consideration for the need of anticoagulant therapy in patients
who develop atrial fibrillation (AF) or flutter and possible
need for antiarrhythmic therapy and electrophysiologic
interventions. Many of these considerations have been
addressed in depth in separate guideline documents.10
Generally, arrhythmic complications increase both morbidity and mortality rates in patients after ACS. Patients
who present with AMI with reduced LVEF (≤40%) have
increased risk of new-onset AF, bradyarrhythmias, and
ventricular arrhythmias.11,12 This risk appears to be increased in those patients who are not revascularized or
receive fibrinolytic therapy compared with those who undergo PCI.11
Recommendation-Specific Supportive Text
1. Ventricular arrhythmias are common after ACS
and more common in patients with reduced LVEF.
MADIT II (Multicenter Automatic Defibrillator
Implantation Trial) demonstrated a 31% reduction
in all-cause mortality (HR, 0.69 [95% CI, 0.510.93]) for prophylactic implantation of a cardiac
defibrillator in patients with an LVEF ≤30% who
were at least 30 days after MI or 3 months after
revascularization for MI and had an anticipated life
expectancy longer than 1 year.2 A mortality benefit
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Table 17. LVEF and Patient Characteristics Defining an
Indication for Prophylactic ICD Implantation for Primary
Prevention in Ischemic Heart Disease
LVEF
Patient Category: All Patients Should
Have Expected Survival of ≥1 y
≤30%
NYHA class I, II, or III2
31%-35%
NYHA class II or III1,3
≤40%
Inducible VT1,4,13
ICD indicates implantable cardioverter-defibrillator; LVEF, left ventricular ejection
fraction; NYHA, New York Heart Association; and VT, ventricular tachycardia.
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for prophylactic ICD implantation has also been
shown in patients with an LVEF ≤35% and New
York Heart Association class II or III HF symptoms,1,3 as well as in patients with inducible ventricular tachycardia or ventricular fibrillation and an
LVEF ≤40%1,4,13 (Table 17).
2. The risk of ventricular arrythmias and sudden cardiac death is highest early after MI, although the
routine implantation of a defibrillator (for primary
prevention) in patients with LV dysfunction early
after MI or CABG has not been associated with
improved survival.14–16 In DINAMIT (Defibrillator in
Acute Myocardial Infarction Trial), ICD implantation led to a 58% reduction in arrhythmic deaths
within 6 to 40 days post MI with ejection fraction
≤35%; however, this was offset by an increase
in nonarrhythmic deaths.16 Sustained episodes
of ventricular tachycardia or ventricular fibrillation
occurring >48 hours after reperfusion are associated with an increased risk of death,12,17 and
the risk of sudden cardiac death is highest in the
first month.5 Patients with ventricular arrhythmias
should first be managed with beta blockers and/or
antiarrhythmic therapy. The benefit of ICD implantation in patients with persistent or sustained ventricular arrhythmias and who are <40 days post
MI remains unclear.15,16,18 A single-center observational study enrolled patients post STEMI (median,
9 days) and referred those with an LVEF ≤40%
for electrophysiologic testing and implanted an
ICD only in those with inducible ventricular tachycardia. Although a randomized comparator arm
was unavailable, 22% of those who underwent
ICD implantation had ventricular tachycardia terminated by the device during the first 12 months.6
The effects of ICD implantation on mortality cannot be definitely ascertained, and more research is
required. Radiofrequency catheter ablation should
be considered in patients with recurrent ventricular tachycardia or ventricular fibrillation followed by
ICD implantation.19 Earlier ICD implantation can be
considered in patients who have an indication for a
permanent pacemaker prior to hospital discharge
and in whom LVEF is not expected to recover, but
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no evidence was observed to definitively demonstrate the safety of this approach.10,20
3. In the VEST (Vest Prevention of Early Sudden
Death) trial, the routine use of a temporary wearable cardioverter-defibrillator did not significantly
reduce the primary endpoint (composite of sudden
death or death from ventricular tachyarrhythmias
at 90 days) in patients with AMI and LVEF ≤35%
(relative risk, 0.67 [95% CI, 0.37-1.21]).7,21 The
secondary endpoint of death from any cause was
lower in the wearable vest group compared with
the no-device group (relative risk, 0.64 [95% CI,
0.43-0.98]); only 12 of 48 patients were wearing
the device at the time of death.7 Greater benefit
was demonstrated in those who were compliant
with the device.21 As such, use of a wearable cardioverter-defibrillator could be considered in highrisk patients with reduced LVEF as a bridge to
consideration for the need for an ICD.
4. Patients with STEMI with second- or third-degree
atrioventricular block have higher in-hospital mortality than those without high-degree atrioventricular block.22,23 Patients who present with ACS with
complete heart block have a higher incidence of
cardiogenic shock, ventricular arrhythmia, and
death.24,25 In a contemporary cohort of patients with
AMI, the incidence of high-degree atrioventricular
block has decreased from 4.2% to 2.1%; however,
increased morbidity and mortality remain despite
reperfusion therapy in those with high-degree atrioventricular block.26,27 A pooled analysis of 30 000
patients found that high-degree atrioventricular
block, asystole, and electromechanical dissociation are infrequent complications of NSTEMI but
are associated with increased short-term mortality.
High-degree atrioventricular block is not considered to be responsible for the increased mortality
but is a surrogate marker of larger infarct size.28
Temporary pacemaker insertion in the setting of
ACS in patients with high-degree atrioventricular
block and other pacer indications has been found
to improve postdischarge survival.8,9,29 Permanent
pacemaker insertion is recommended with unresolved high-degree atrioventricular block that persists >72 hours.20
9.3. Pericarditis Management After MI
Synopsis
The diagnostic criteria for post-MI pericarditis are displayed in Table 18. Pericarditis that occurs early after MI
typically arises 1 to 3 days after a transmural event and
is presumed to be inflammatory in nature due to adjacent
myocardial necrosis. These cases of early pericarditis are
typically transient, lasting several days, and will resolve
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2025 Acute Coronary Syndromes Guideline
Table 18. Clinical Criteria for Diagnosis of Pericarditis
Friction pericardial rub on auscultation
Electrocardiographic evidence such as classic PR-segment depression or
diffusive concave ST-segment elevations, or in the setting of MI, persistent
ST-segment elevations or dynamic T-wave changes
New or growing pericardial effusion on echocardiography
MI indicates myocardial infarction.
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with conservative therapy. Acetaminophen can be given
for symptomatic relief. A second form of pericarditis may
occur weeks after MI (Dressler’s syndrome) and is believed to be immune-mediated as a response to pericardial irritation or damage, such as in the setting of any
degree of hemopericardium.1,2 These cases of late pericarditis often require additional therapy (Table 19). Given
the rarity of post-MI pericarditis (0.1%-0.5%) in the era
of early coronary reperfusion therapy,3 dedicated RCTs
of high-dose aspirin are lacking, and data are extrapolated from studies of the heterogeneous diagnosis of acute
pericarditis.4 Furthermore, RCTs of colchicine were performed on a background of high-dose aspirin therapy.5–7
If symptoms persist despite standard supportive therapy
in early pericarditis and in any late pericarditis, high-dose
aspirin may be used to reduce symptoms.4 The use of
colchicine should also be considered to reduce symptoms and decrease risk of recurrence8,9; suggested dosing is summarized in Table 19. The value of a loading
dose of colchicine in this setting is unclear. Routine use
of high-dose aspirin or colchicine is not indicated for the
management of asymptomatic pericardial effusions.10,11
Glucocorticoids and nonsteroidal anti-inflammatory
drugs (other than aspirin) are potentially harmful due to
possible increase in risk of recurrent MI or impaired myocardial healing and risk of rupture.12,13
9.4. Management of LV Thrombus After MI
Synopsis
LV thrombus typically occurs in the setting of large anterior
STEMI and can lead to thromboembolic complications, including stroke and systemic embolization. In the era of PCI,
the incidence of LV thrombus after ACS has decreased
and is estimated to be <5% to 10% in the post-MI population.1–3 Limited RCT data are available on the contemporary
Table 19. Additional Therapy for Persistent/Late Pericarditis
Symptoms
Medical Therapy
Dosing Schedule
High-dose aspirin
500-1000 mg every 6-8 h until symptoms improve
Colchicine
0.5-0.6 mg once* or twice daily for 3 mo
*Daily dosing should be used in patients who weigh <70 kg and further adjusted in patients with stage 4-5 kidney disease, severe hepatic impairment, or
with concomitant P-glycoprotein and/or moderate and severe CYP3A4 inhibitors.
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10. IN-HOSPITAL ISSUES IN THE
MANAGEMENT OF ACS
10.1. Cardiac Intensive Care Unit
Recommendation for CICU
COR
1
LOE
Recommendation
C-EO
1. Patients with ACS and with ongoing angina, hemodynamic instability, uncontrolled arrhythmias, suboptimal reperfusion, or cardiogenic shock should
be admitted to a CICU to reduce cardiovascular
events.
Synopsis
The nurse-to-patient ratio in the CICU should be sufficient to provide (1) continuous electrocardiographic
rhythm monitoring, (2) frequent assessment of vital signs
and mental status, and (3) ability to perform rapid cardioversion and defibrillation for arrhythmias.1,2 Some hospitals may not have a dedicated CICU but rather care
for patients with MI within a general multipurpose ICU;
this approach requires trained providers with sufficient
expertise in the care of cardiac patients.
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Diagnosis Is Made With Presence of Pleuritic Chest Pain and ≥1 of the
Following Criteria:
management of LV thrombus, and current management is
based mostly on retrospective and observational data and
expert consensus. Patients at highest risk for LV thrombus include those with anterior STEMI involving the left
anterior descending artery, LVEF <30% (especially in the
presence of an LV aneurysm), and longer times to reperfusion. An echocardiogram is the recommended imaging
modality for diagnosis, given its wide accessibility and low
cost.4 Cardiac MRI is more sensitive for detection of LV
thrombus and may be considered when there is high clinical suspicion and echocardiogram results are inconclusive.
LV thrombus may form later during hospitalization or after
discharge; therefore, repeat imaging can sometimes detect LV thrombus in high-risk patients.5 Because DAPT is
recommended for most patients early after ACS, the addition of an anticoagulant for LV thrombus needs to be
considered in the context of the patient’s overall bleeding
risk versus their risk of an embolic event. Most patients
with LV thrombus will warrant anticoagulation for a period of 3 months, at which time the presence of residual
thrombus can be assessed by repeat imaging to help determine whether a more prolonged course is warranted.1
Although direct oral anticoagulants (DOAC) are routinely
used in clinical practice, there are limited data comparing
the efficacy of a DOAC versus vitamin K antagonist in the
setting of LV thrombus. Observational studies and small
RCTs have suggested that DOAC may be noninferior to
vitamin K antagonist with respect to mortality, stroke, or LV
thrombus resolution, and DOACs may offer an improved
bleeding profile.6 The practical management of LV thrombi
is more completely addressed in other documents.1,6
CLINICAL STATEMENTS
AND GUIDELINES
Rao et al
2025 Acute Coronary Syndromes Guideline
Recommendation-Specific Supportive Text
1. Admission to the CICU and optimal length of
stay in the CICU after an MI should be based on
patients’ risk profile and clinical stability, while
considering the patient’s baseline cardiac risk and
comorbidities. Patients with ACS with continuing/
ongoing angina, hemodynamic instability, uncontrolled arrhythmias, or a large MI with HF, cardiogenic shock, or both, should be admitted to a
CICU.1,2 Patients with ongoing ischemic symptoms
should be preferentially triaged for cardiac catheterization whenever possible. Stable patients with
ACS and without recurrent ischemia, significant
arrhythmias, pulmonary edema, or hemodynamic
instability do not need CICU admission and can
be admitted to an intermediate care or telemetry
unit. Clinical predictors may be useful for helping
identify patients who will require CICU care. For
example, the ACTION ICU risk score for CICU
admission integrates 9 variables on presentation to
the ED including: signs or symptoms of HF, initial
heart rate, initial SBP, initial troponin, initial serum
creatinine, prior revascularization, chronic lung disease, ST-segment depression, and age >70 years.3
10.2. Management of Anemia in ACS
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Recommendation for Management of Anemia in ACS
Referenced studies that support recommendation are summarized in
the Evidence Table.
COR
LOE
Recommendation
2b
B-R
1. In patients with ACS and acute or chronic anemia,
blood transfusion to achieve a hemoglobin level
≥10 g/dL may be reasonable to reduce
cardiovascular events.1
Synopsis
Anemia is common in patients with ACS and is associated with worse short- and long-term outcomes.2–4
Anemia is associated with adverse outcomes irrespective of whether the anemia is chronic and due to comorbid conditions, or acute and the result of bleeding
related to antithrombotic therapy and/or invasive procedures. The adverse effects of anemia may be due to
decreased myocardial oxygen delivery, increased myocardial oxygen demand due to increased cardiac output,
or the avoidance of potentially beneficial antithrombotic
drugs and/or procedures. In observational studies, blood
transfusion has been associated with worse clinical outcomes.5–8 Randomized trials in medically ill patients and
those undergoing cardiac surgery have demonstrated
similar or better outcomes with a restrictive transfusion
strategy (targeting a blood hemoglobin level around
8 g/dL) than with a liberal transfusion strategy
(targeting a blood hemoglobin level around 10 g/dL).9–11
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However, randomized trial evidence for populations with
ACS suggests possible clinical benefit for a more liberal
transfusion strategy targeting a hemoglobin level above
10 g/dL compared with targeting a hemoglobin level
above 7 g/dL to 8 g/dL.1,12,13
Recommendation-Specific Supportive Text
1. The MINT (Myocardial Ischemia and Transfusion)
trial randomly assigned 3504 patients with acute
STEMI or NSTEMI and anemia with a blood hemoglobin level of <10 g/dL (13% with recent bleeding) to a restrictive transfusion strategy (transfusing
if the hemoglobin level was <7-8 g/dL) or a liberal
transfusion strategy (transfusing if the hemoglobin
level was <10 g/dL).1 Patients were ineligible for
enrollment if they had uncontrolled bleeding, were
receiving palliative treatment, or were scheduled to
have cardiac surgery. Transfusion could be delayed
for patients with volume overload or until day of
dialysis in patients with end-stage renal disease.
The primary outcome of 30-day death or recurrent
MI occurred in 16.9% of patients in the restrictive strategy and 14.5% of patients in the liberal
strategy (relative risk, 1.15 [95% CI, 0.99-1.34];
P =0.07). Death occurred in 9.9% of patients in
the restrictive strategy and 8.3% of patients in
the liberal strategy (relative risk, 1.19 [95% CI,
0.94-1.49]), and cardiac death occurred in 5.5%
of patients in the restrictive strategy and 3.2% of
patients in the liberal strategy (relative risk, 1.74
[95% CI, 1.26-2.40]). Although the MINT trial did
not demonstrate a statistically significant reduction in its primary endpoint, the results suggest
that a liberal blood transfusion strategy targeting
a hemoglobin level around 10 g/dL may provide
short-term clinical benefit over a restrictive transfusion strategy targeting a hemoglobin level above 7
g/dL or 8 g/dL in patients with AMI and anemia.
10.3. Telemetry and Length of Stay
Recommendation for Telemetry and Length of Stay
COR
LOE
Recommendation
1
C-LD
1. In patients with ACS, telemetry monitoring is
recommended to reduce cardiovascular events
with duration determined by cardiac risk.1,2
Synopsis
Advances in vascular access methods, coronary revascularization, and concomitant medical therapies have
contributed to shortening length of stay and further
facilitated changes in discharge patterns after PCI in
the setting of ACS. There remains limited evidence
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Recommendation-Specific Supportive Text
1. The number of studies addressing telemetry duration are few and the focus has been on arrhythmia
monitoring, not continuous ST-segment monitoring. Continuous ST-segment monitoring can
be considered for higher-risk patients, including
those with suspected ischemia who are not yet
revascularized.1,10–14 Patients with ACS who are
at low risk for cardiac arrhythmias require rhythm
monitoring for ≤24 hours or until coronary revascularization (whichever comes first) in a telemetry
unit, while individuals at intermediate to high risk
for cardiac arrhythmia may require rhythm monitoring for >24 hours in a telemetry unit or in an
intermediate care unit, depending on the clinical presentation, degree of revascularization, and
early postrevascularization course with input from
the treating cardiologist.10,12–14
10.4. Noninvasive Diagnostic Testing Prior to
Hospital Discharge
Recommendation for Noninvasive Diagnostic Testing Prior to Hospital
Discharge
COR
1
LOE
Recommendation
C-LD
1. In patients with ACS, an assessment of LVEF is
recommended prior to hospital discharge to guide
therapy and for risk stratification.1–3
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Synopsis
In patients with ACS, LV function should be routinely
evaluated in patients prior to hospital discharge to help
guide therapy and for risk stratification.1–3 Transthoracic
echocardiography is generally the preferred modality because it is noninvasive and can provide a comprehensive
assessment of ventricular and valvular function, as well as
possibly detect LV thrombus or mechanical complications.
Transthoracic echocardiography is therefore strongly preferred for all patients hospitalized with STEMI because
complications may be more likely to be present. In patients where transthoracic echocardiography is nondiagnostic, cardiac magnetic resonance imaging is a reasonable alternative in clinically stable patients. Alternatively,
LV function and some mechanical complications can be
assessed invasively with left ventriculography in the cardiac catheterization laboratory, but other data regarding
valvular function and wall motion are best evaluated with
noninvasive methods like transthoracic echocardiography
or cardiac magnetic resonance imaging. LV function may
also be estimated noninvasively by myocardial perfusion
imaging testing, but this will also provide incomplete information regarding the presence or absence of other
complications of MI. For patients in whom LV function is
found to be reduced, a repeat echocardiogram should be
performed in 6 to 12 weeks to further guide treatment
decisions and for consideration of need for an ICD.4,5
Recommendation-Specific Supportive Text
1. LV function should be routinely evaluated in
patients with ACS prior to hospital discharge
because LVEF guides therapeutic interventions
and facilitates risk stratification. The diagnosis of
LV dysfunction is important because it may trigger consideration for the initiation or optimization
of guideline-directed therapeutic interventions for
patients with HF or depressed LV function. It also
helps identify patients with reduced LVEF who may
require consideration for future primary prevention
implantation of an ICD. Besides LVEF, transthoracic echocardiography facilitates the assessment
of regional wall motion abnormalities, valvular function, mechanical complications,4 and LV thrombus.5
In cases in which LV function cannot be adequately
assessed despite the use of contrast echocardiography, cardiac magnetic resonance is the preferred
imaging modality for clinically stable patients.6–9
10.5. Discharge Planning
10.5.1. Patient Education
Synopsis
Patient education is universally valued and aims to deliver information from clinicians to patients to improve
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AND GUIDELINES
regarding the optimal length of stay after MI. Patients
with STEMI represent a higher risk cohort who may
require longer length of stay. Available data suggest
that an early discharge strategy of <3 days from admission is not associated with increased mortality for
low-risk patients after STEMI who have undergone
PCI.3–8 The Zwolle score has been recommended as
a clinical tool to help identify patients after PPCI in
STEMI at low risk of death (low-risk patients, score
≤3) who can potentially be discharged earlier from the
hospital (48 to 72 hours). Predictors of mortality in the
Zwolle score include age, Killip class, postprocedural
TIMI Flow Grade, 3-vessel disease, anterior infarction,
and ischemic time.3 Optimal length of stay in the setting of NSTE-ACS has been less rigorously studied.
Small retrospective studies have suggested safety of
very early or same-day discharge after PCI for patients
with ACS, with most (71%) of same-day discharge
being troponin-negative.9 Patients being considered
for early discharge should be clinically stable without
evidence of ongoing ischemia, acute kidney injury, LV
dysfunction, HF, and procedural complications and with
adequate postdischarge support.8 Hospitals and care
providers should ensure that patients have access to
postdischarge prescription medications and adequate
follow-up.
CLINICAL STATEMENTS
AND GUIDELINES
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health behavior and long-term health-related outcomes.
Clinicians are well positioned to engage in meaningful
dialogue with patients who have experienced an ACS
event about secondary prevention and building self-care
skills to manage their condition (Table 20). Recovery
represents a teachable moment to provide structured
education, including priming the patient to attend cardiac rehabilitation (CR). Systematic reviews of educational interventions targeting secondary prevention in
patients with coronary heart disease, many of whom
have ACS, have demonstrated effectiveness in improving disease-related knowledge, healthy behaviors (eg,
smoking cessation, physical activity, healthy dietary behavior), and medication adherence.1–3 The magnitude of
the effect on each of these outcomes varies by study.
Beyond improved knowledge and behavior change, the
impact of individualized education for patients with ACS
on morbidity and mortality is less clear. A shortcoming of
published educational intervention studies to date is that
the interventions are markedly heterogeneous but vary in
intensity, duration, delivery mode, resources needed, and
outcomes measured. Currently, insufficient comparative
data are available to guide clinicians about which specific educational interventions are best. However, evidence supports the use of individualized goal setting that
demonstrates respect for the patient and their circumstances, structured content that is culturally appropriate,
and clearly defined outcomes.4 Table 20 lists the components that should be discussed with ACS patients at the
time of hospital discharge.
10.5.2. Postdischarge Follow-Up and Systems of
Care Coordination
2025 Acute Coronary Syndromes Guideline
ethnic groups, and patients who require ICU services
during their index hospitalization are particularly at risk
for readmission.3 Quality improvement programs such as
the Hospital to Home Initiative7 or the AMI Toolkit8 provide resources to assist clinicians decrease readmission
rates and improve medication and CR adherence through
increased provider communication and care coordination. Transitional care interventions that leverage different
types of support (eg, hospital-initiated support, patient and
family education delivered before and after discharge, or
community-based or chronic disease management models of care) are examples of ways to reduce risk of readmission.9 Hospital-initiated support interventions are associated with reduced mortality rates at 3 months and 1 year
as well as a reduction in 30-day readmission rates among
patients with AMI.9,10 Multicomponent integrated care (≥2
quality improvement strategies targeting different domains of the health care system, health care professionals,
or patients) as compared with usual care has been associated with reduction of all-cause death, cardiovascular
mortality, and all-cause hospitalization.11 Emerging digital
health interventions hold promise to improve the transition
from hospital to home. For additional recommendations on
nutrition, physical activity, smoking cessation, and alcohol
and substance use, refer to the “2023 AHA/ACC/ACCP/
ASPC/NLA/PCNA Guideline for Management of Patients
With Chronic Coronary Disease.”12 Table 21 summarizes
the recommended guidance for hospital discharge.
10.5.3. Cardiac Rehabilitation
Recommendations for CR
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
LOE
Recommendations
1
A
1. Patients with ACS should be referred to an
outpatient CR program prior to hospital
discharge to reduce death, MI, hospital readmissions, and improve functional status and QOL.1–4
2a
B-R
2. In patients with ACS, a home-based CR program
is a reasonable alternative to a center-based CR
program to improve functional status and QOL.5–9
Synopsis
Transition from the hospital to home is a critical period for
patients with ACS because approximately 1 in 5 patients
are readmitted within 30 days of discharge.1–6 Women,
individuals from traditionally underrepresented racial and
Table 20. Essential Components of Patient Education
Reason for hospitalization (explain reason for admission, diagnostic tests,
procedural results)
Tailored discussion of lifestyle modifications (AHA’s Life’s Essential 8)5
Medications (written and verbal instructions including purpose, dose,
frequency, potential adverse effects of each medication; refill instructions;
changes to prehospital regimen; importance of adherence)
Symptom management (what to monitor for and actions to take should
symptoms recur, including whom to call)
Returning to daily routine (when to resume physical activity, sexual activity,
work, and travel)
Psychosocial considerations (open dialogue about symptoms of depression
and anxiety)
Follow-up care (future appointments with cardiology, CR, additional testing
postdischarge)
AHA indicates American Heart Association; and CR, cardiac rehabilitation.
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Synopsis
CR is a multifaceted and comprehensive outpatient intervention that is considered the standard of care for secondary prevention of CVD. The primary goals of CR are
modifying CVD risk factors and improving patient functional capacity and QOL with the goal of reducing subsequent morbidity and mortality. Through a combination of
monitored exercise training, health and nutrition education,
psychological support, and personalized patient assessment, including medication optimization (Figure 10), CR
has been shown to lower the risk of cardiovascular and
all-cause death, reduce hospital readmissions, and to be
cost-effective.10,11 Despite its proven benefits, CR is underutilized and referral rates to CR are low, especially for womCirculation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
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2025 Acute Coronary Syndromes Guideline
Table 21. Guidance for ACS Discharge: Best Practices
Patient centered, verbally and in writing in patient/caregiver preferred language
Shared decision-making regarding assessment of goals and preferences should be discussed with patient/caregiver
Clinical assessment
Address comorbidities and risk factors for recurrent events
Assess for presence of ongoing ischemic symptoms, using standardized instrument ideally embedded into EHR
Assess risk for bleeding related to medications or procedural site
Assess need for additional testing (eg, repeat echocardiogram, staged PCI)
Assess whether vaccinations are current (eg, influenza)
Perform medication reconciliation, including a prescription for sublingual nitroglycerin, unless contraindicated
Patient/caregiver assessment
Assess capacity for patient/caregiver for self-care (eg, secondary prevention, symptom monitoring, following plan of
care, lifestyle changes, contact information for continuing care team)
Provide verbal and written educational information related to self-care
Use teach-back method to confirm understanding of self-care
Use teach-back method for patient/caregiver understanding of medication adherence and treatment regimen
Referrals
Confirm referral to CR
Provide educational materials related to CR including contact information
Social determinants of health
Assess and address barriers to obtaining and taking prescribed medications, to include referral to pharmacy
assistance programs or social worker as appropriate
Assess and address barriers to attending CR, including viability of home-based or hybrid CR
ACS indicates acute coronary syndromes; CR, cardiac rehabilitation; EHR, electronic health record; and PCI, percutaneous coronary intervention.
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en and members of traditionally underrepresented groups.8
Factors that contribute to this overall low enrollment rate
include a poor utilization of a centralized method for referral
via the electronic health record, inadequate communication
between treatment teams, and perceived inconvenience as
well as associated costs for the patient.8 To increase the
utilization of CR, patients should be referred to CR during hospitalization for ACS and prior to discharge.12 To improve access for patients who live in rural locations and in
areas with no center-based CR, home-based CR options
should be considered. These home-based CR programs
have similar shorter-term safety and clinical outcomes (eg,
improvements in exercise capacity, QOL, blood pressure,
cholesterol) as center-based CR.13–15 More intensive CR
programs have been developed with a goal of expanding
the benefits of traditional CR programs through additional exercise and education sessions, as well as placing a
greater focus on diet and lifestyle factors.16–18 Although
improved outcomes have been described with an intensive
program,16,19 the studies are observational in nature. Both
traditional and intensive CR programs remain underutilized,
so the primary emphasis should be on enrollment and adherence to any CR program.20
Recommendation-Specific Supportive Text
1. Exercise-based CR programs are associated with
improved survival and reduced risk of reinfarction in
patients after AMI.1–4 CR can be enhanced as a component of a multifactorial rehabilitation program with
risk factor education and counseling. Patients with
ACS who participate in CR have significantly better
outcomes compared with those who do not.1,21,22 In
a meta-analysis of 85 RCTs of exercise-based CR
in patients with coronary heart disease, the intervention reduced risk of MI, reduced all-cause hospitalization, reduced health care costs, and improved
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health-related QOL outcomes over 12 months of
follow-up.1 Longer follow-up suggested reductions in
cardiovascular mortality.1,4 CR is particularly beneficial
in older patients with CAD, a group that is at a higher
risk of losing independence and functioning.23–26
2. To overcome challenges that have prevented greater
patient participation, new strategies and innovative
models that utilize digital health tools are emerging
to meet the evolving needs of CR patients. CR programs have traditionally been delivered via centerbased CR. These programs require patients to be
physically present at a facility located in a hospital
or outpatient center, which limits access for many
patients, especially women and some racial and ethnic groups.9,27,28 A review of 23 RCTs of home- and
center-based CR found that these programs tend
to implement the same core components.13 These
include patient assessment of current medical history, exercise training, dietary counseling, risk factor
management (eg, smoking, lipids, blood pressure,
weight, diabetes), and psychological intervention.
Comparison of studies in home- and center-based
CR indicate a similar improvement in QOL and no statistically significant difference in the all-cause mortality rate up to 12 months after the intervention.5,6
However, more RCTs are needed with home-based
CR in patients with ACS because of an evidence
gap (especially in high-risk patients) in assessing
the safety of home-based CR in patients at high
risk for recurrent ischemic events, as well the impact
of a home-based rehabilitation strategy on clinical
outcomes such as cardiovascular death, recurrent
MI, and rehospitalization.29 Advances in technology
and remote monitoring may help to improve the efficacy and safety of this approach. Hybrid models that
combine elements of both center- and home-based
programs may also offer benefits.
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Communication
2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
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Figure 10. Core Components of Cardiac Rehabilitation.
Adapted with permission from Sandesara et al.30 Copyright 2015 American College of Cardiology Foundation.
11. DISCHARGE: LONG-TERM
MANAGEMENT AND SECONDARY
PREVENTION
11.1. DAPT Strategies in the First 12 Months
Postdischarge
Recommendations for DAPT Strategies in the First 12 Months
Postdischarge
Referenced studies that support recommendations are summarized in
the Evidence Table.
COR
LOE
Recommendations
Recommendations for DAPT Strategies in the First 12 Months
Postdischarge (Continued)
COR
LOE
A
2. In patients with ACS who have tolerated DAPT with
ticagrelor, transition to ticagrelor monotherapy ≥1
month post PCI is useful to reduce bleeding risk.7–11
A
3. In patients at high risk of gastrointestinal
bleeding, a proton pump inhibitor (PPI) is recommended in combination with DAPT, oral anticoagulants, or both to reduce risk of bleeding.12–15
2b
B-R
4. In patients with ACS undergoing PCI, deescalation of DAPT (switching from ticagrelor or
prasugrel to clopidogrel) after 1 month may be
reasonable to reduce bleeding risk.16–20
2b
B-R
5. In patients with ACS undergoing PCI who are at
high bleeding risk, transition to single antiplatelet
therapy (aspirin or P2Y12 inhibitor) after 1 month
may be reasonable to reduce bleeding risk.21
1
1
Default Duration of DAPT
1
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A
1. In patients with ACS who are not at high bleeding
risk, DAPT with aspirin and an oral P2Y12 inhibitor should be administered for at least 1 year to
reduce MACE.1–6
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Recommendations
Bleeding Reduction Strategies
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The addition of an oral P2Y12 inhibitor to aspirin (DAPT)
reduces the risk of early and late thrombotic events
among patients with ACS regardless of whether they
are managed with an invasive strategy.1–3 Notwithstanding these salutary benefits, prolonged exposure to DAPT
results in excess bleeding that may lead to DAPT interruption,22 which in turn may increase the risk of recurrent ischemic events.23 Identifying individuals most likely
to realize a net clinical benefit or harm from prolonged
DAPT has emerged as an important clinical priority.
Several tools have been developed that predict the risk
of ischemic and/or bleeding events and may be useful
when considering how best to personalize care for an
individual patient.24–27 Moreover, alternative antiplatelet
strategies have been compared with conventional DAPT
with the intent to reduce bleeding while maintaining ischemic efficacy. Growing evidence suggests that a strategy
of aspirin discontinuation with ticagrelor monotherapy
reduces bleeding.7–11 Although clopidogrel monotherapy
has been studied,28,29 interpatient variability in pharmacodynamic response to clopidogrel is substantial30 and may
increase thrombotic risk in certain individuals. To that
end, a strategy of clopidogrel monotherapy may increase
risk of MACE in patients after ACS when compared with
more prolonged DAPT.29 Additional approaches include
aspirin monotherapy31,32 or a strategy of “de-escalation”
(ie, switching from ticagrelor or prasugrel to clopidogrel),16–20 although the safety of these strategies in terms
of their effects on risk of MACE is less firmly established.
Efficacy and safety of shorter DAPT strategies have not
been rigorously studied in patients not undergoing PCI.
Figure 11 summarizes the guideline recommendations
for DAPT management in patients with ACS during the
first 12 months post discharge.
Recommendation-Specific Supportive Text
1. Patients with ACS are characterized by a sustained prothrombotic state,33 thus highlighting the
need for continued antithrombotic therapy beyond
the index presentation. The double-blind placebocontrolled CURE (Clopidogrel in Unstable Angina
to Prevent Recurrent Events) trial (n=12 562)
demonstrated that DAPT with clopidogrel yields a
consistent reduction in both early and late composite ischemic events as compared with aspirin alone
among patients with NSTE-ACS who were primarily managed medically.3,34 The treatment effect was
consistent among those treated with or without
revascularization.4 Subsequent studies showed
that DAPT with prasugrel or ticagrelor administered for 1 year provides incremental reductions
in ischemic events, albeit with excess bleeding,
as compared with clopidogrel.1,2 Although concordant benefits were also observed among trial
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participants requiring surgical revascularization, the
safety and efficacy of DAPT should be considered
in the context of CABG as a postrandomization
event and the high proportion of patients who did
not resume study drug after surgery.4–6 An important consideration in extending the results of clinical trials that established the benefits of DAPT to
contemporary cohorts is that patients at elevated
risk for bleeding were typically excluded in early
studies. Therefore, the default strategy for a minimum DAPT duration of 1 year is most applicable to
those patients without high bleeding risk presenting with ACS. Moreover, the choice of P2Y12 inhibitor may vary in relation to treatment approach, as
described in Section 4.3.2, “Oral P2Y12 Inhibitors
During Hospitalization.” In select patients who have
tolerated DAPT, it may be reasonable to extend
treatment beyond 1 year after considering risks for
long-term bleeding and thrombosis.35–37
2. Results from several randomized trials have consistently shown that aspirin withdrawal followed
by ticagrelor monotherapy after 1 to 3 months
of ticagrelor-based DAPT results in less bleeding without clear excess in MACE, as compared
with continued DAPT among patients with ACS
undergoing PCI.7–11 Although studies examining
this strategy were characterized by relatively low
rates of ischemic events, study-level38 and individual patient data pooled analyses39–41 have yielded
similar results. Although data with clopidogrel have
been mixed, concerns have been raised that a
strategy of clopidogrel monotherapy started 1 to
2 months after PCI may increase risk of MACE
in patients with ACS when compared with longer
DAPT.29 It remains unknown whether this may be
explained by excess thrombotic risk in patients
displaying inadequate platelet inhibition to clopidogrel, observed in 30% to 40% of patients after
PCI.30,42 Results from a randomized trial showed
that a strategy of P2Y12 inhibitor discontinuation
followed by aspirin alone after 6 months of DAPT
resulted in excess thrombotic risk among patients
with ACS undergoing PCI (n=2712; 38% STEMI),
albeit with less bleeding.32 Similar findings were
observed with earlier P2Y12 inhibitor discontinuation 3 months after PCI.31,43 Although the on-treatment pharmacodynamic effects of ticagrelor and
prasugrel are similar, the safety of a strategy of
prasugrel monotherapy has not been established
in patients ≥1 month post ACS; low-dose prasugrel
monotherapy (3.75 mg daily) in Japanese patients
very early after PCI with ACS or at high bleeding
risk may increase 30-day MACE compared with
DAPT.44
3. PPIs reduce the risk of gastrointestinal bleeding
among patients receiving aspirin,14 DAPT,13 or an
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Synopsis
2025 Acute Coronary Syndromes Guideline
2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
Rao et al
Figure 11. DAPT Strategies in the First 12 Months Postdischarge.
Colors correspond to Class of Recommendation in Table 2. *High bleeding risk discussed in Section 11.1, “Recommendation-Specific Supportive
Text” item 5, and outlined in Table 22. ACS indicates acute coronary syndromes; DAPT, dual antiplatelet therapy; OAC, oral anticoagulant; PCI,
percutaneous coronary intervention; and SAPT, single antiplatelet therapy.
Downloaded from http://ahajournals.org by on February 28, 2025
oral anticoagulant.12,15 Because the conversion of
clopidogrel to its active metabolite and the metabolism of certain PPIs depend on some common
hepatic enzymes (eg, CYP2C19), the potential for a
drug-drug interaction exists when both agents are
coadministered. The results of several ex vivo studies
found that clopidogrel-induced platelet inhibition is
attenuated with use of certain PPIs, a pharmacodynamic effect that is most pronounced with omeprazole.45,46 Nonetheless, results from a double-blind,
placebo-controlled randomized trial showed no
significant differences in ischemic events between
omeprazole versus placebo among patients treated
with clopidogrel, but PPI use markedly decreased
the risk of gastrointestinal bleeding.13 Moreover,
post hoc analyses from several randomized trials have shown that ischemic risk is not increased
when a clinically indicated PPI is used with clopidogrel.47,48 Importantly, the antiplatelet effects and
clinical efficacy of ticagrelor and prasugrel are not
appreciably modified with concomitant PPI use.48–50
Therefore, it is recommended to administer a PPI in
patients with ACS at elevated bleeding risk treated
with DAPT or oral anticoagulant.
4. De-escalation implies modulating DAPT intensity
by switching from ticagrelor or prasugrel to clopidogrel.51 De-escalation can be guided by the results
of platelet function assays that quantify the degree
of platelet inhibition among patients treated with
clopidogrel. Patients with adequate response may
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continue to receive clopidogrel, whereas nonresponders are switched to a more potent P2Y12
inhibitor. Clopidogrel responsiveness may also be
inferred with use of genotyping assays that identify polymorphisms in genes involved in clopidogrel metabolism.52 Clinical trials examining guided
de-escalation after PCI have either shown a lack
of benefit,16 noninferiority,20 or reductions in minor
bleeding17 versus conventional DAPT. By contrast, unguided de-escalation is performed without
antecedent knowledge of platelet responsiveness.
Randomized trials have suggested that unguided
de-escalation 1 month after PCI reduces bleeding
without incurring ischemic risk as compared with
longer term prasugrel- or ticagrelor-based DAPT.18,19
Pooled analyses have shown that de-escalation
(guided or unguided) yields comparable efficacy to
DAPT with respect to ischemic events while reducing
bleeding.53,54 However, trials of ticagrelor and prasugrel have suggested that the benefit of more potent
P2Y12 inhibitor therapy extends beyond the early
phase post ACS, but with increased bleeding.1,2,55
5. In the MASTER DAPT (Management of High
Bleeding Risk Patients Post Bioresorbable Polymer
Coated Stent Implantation With an Abbreviated
Versus Standard DAPT Regimen) trial, patients at
high risk of bleeding who had completed a 4-week
course of DAPT after successful PCI with drugeluting stents were randomly allocated to single
antiplatelet therapy or more prolonged DAPT (≥2
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2025 Acute Coronary Syndromes Guideline
Table 22. Academic Research Consortium High Bleeding Risk Criteria After PCI
CLINICAL STATEMENTS
AND GUIDELINES
Major Criteria26
Minor Criteria
Age ≥75 y
Anticipated use of long-term oral anticoagulation (Section 11.1.1, “Antiplatelet
Therapy in Patients on Anticoagulation Postdischarge”)
Severe or end-stage CKD (eGFR <30 mL/min)
Moderate CKD (eGFR 30-59 mL/min)
Hemoglobin level <11 g/dL
Hemoglobin level 11-12.9 g/dL for men and 11-11.9 g/dL for women
Spontaneous bleeding requiring hospitalization or transfusion in the past 6 mo
or at any time, if recurrent
Spontaneous bleeding requiring hospitalization or transfusion within the past
12 mo not meeting the major criterion
Moderate or severe baseline thrombocytopenia (platelet count <100×109/L)
Chronic bleeding diathesis
Liver cirrhosis with portal hypertension
Long-term use of oral NSAIDs or steroids
Active malignancy (excluding nonmelanoma skin cancer) within the past 12 mo
Previous spontaneous ICH (at any time)
Any ischemic stroke at any time not meeting the major criterion
Previous traumatic ICH within the past 12 mo
Presence of a brain arteriovenous malformation
Moderate or severe ischemic stroke within the past 6 mo
Nondeferrable major surgery on DAPT
Recent major surgery or major trauma within 30 d before PCI
The presence of at least 1 major or 2 minor criteria helps to identify those at increased risk of bleeding. Modified with permission from Urban et al.26 Copyright 2019
American Heart Association, Inc.
CKD indicates chronic kidney disease; DAPT, dual antiplatelet therapy; eGFR, estimated glomerular filtration rate; NSAID, nonsteroidal anti-inflammatory drugs; ICH,
intracranial hemorrhage; and PCI, percutaneous coronary intervention.
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additional months).21 In the absence of oral anticoagulant use, the choice of discontinuing aspirin or
P2Y12 inhibitor and the choice of P2Y12 inhibitor
was at the discretion of the treating physician. An
oral anticoagulant was used in 36.4% of patients,
and clopidogrel monotherapy was selected in
53.9% of patients randomized to abbreviated
DAPT. Compared with standard therapy, an abbreviated antiplatelet strategy demonstrated noninferiority with respect to composite ischemic events
and superiority regarding clinically relevant bleeding
over 1 year. Among patients with ACS (n=1780;
30% STEMI) allocated to an abbreviated strategy,
clinicians selected a potent P2Y12 inhibitor with
ticagrelor use in approximately 25% of patients.56
Results in the ACS cohort were qualitatively consistent with the overall trial results with respect to both
ischemic and bleeding outcomes. Although the trial
demonstrated noninferiority for abbreviated DAPT
with respect to MACE in patients at high bleeding
risk, it was underpowered to determine the relative safety of discontinuing aspirin versus P2Y12
inhibitor. Multiple studies have identified clinical
and laboratory predictors of bleeding and/or ischemic risk.24–27 The Academic Research Consortium
determined 20 correlates of bleeding and proposed
a consensus-based definition of high bleeding risk
as the presence of having at least 1 major or 2
minor criteria at time of PCI (Table 22).26
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11.1.1. Antiplatelet Therapy in Patients on
Anticoagulation Postdischarge
Recommendation for Antiplatelet Therapy in Patients on
Anticoagulation Postdischarge
Referenced studies that support recommendation are summarized in
the Evidence Table.
COR
1
LOE
Recommendation
B-R
1. In patients with ACS who require oral
anticoagulant therapy, aspirin should be
discontinued after 1 to 4 weeks of triple
antithrombotic therapy, with continued use of a
P2Y12 inhibitor (preferably clopidogrel) and an
oral anticoagulant to reduce bleeding risk.*1–5
*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery
Revascularization.”6
Synopsis
Patients after ACS may frequently have indications for
anticoagulant therapy, including AF, venous thromboembolism, and prosthetic heart valves. Bleeding risks
are increased in the setting of triple therapy with the
combination of aspirin, P2Y12 inhibitor, and anticoagulant. Therefore, the benefits of these therapies must be
weighed against the risk of bleeding. A growing number of studies have demonstrated the overall safety of
a strategy of aspirin discontinuation 1 to 4 weeks after
ACS or PCI in patients who require anticoagulation after
ACS.1–5 For most patients, a DOAC will be preferred over
a vitamin K antagonist due to their favorable efficacy and
safety profile.7 Trials of more potent P2Y12 inhibitors
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2025 Acute Coronary Syndromes Guideline
(ie, prasugrel and ticagrelor) excluded patients requiring
long-term anticoagulation; therefore, clopidogrel is generally favored as the P2Y12 inhibitor in this setting for
most patients. The decision whether to continue anticoagulant with or without antiplatelet therapy >12 months
after ACS is addressed in the “2023 AHA/ACC/ACCP/
ASPC/NLA/PCNA Guideline for the Management of
Patients with Chronic Coronary Disease.”8
Recommendation-Specific Supportive Text
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1. Several RCTs have demonstrated that the discontinuation of aspirin 1 to 4 weeks after PCI
reduces the risk of bleeding in patients with AF
with an indication for DAPT and an oral anticoagulant.1–5 Although individual studies were not
powered for ischemic endpoints, meta-analyses
across randomized trials suggest no difference in
mortality, stroke, and overall MACE when aspirin
is discontinued for patients on an oral anticoagulant, albeit with a marginal apparent increase in
MI and stent thrombosis.9–14 An analysis of stent
thrombosis rates suggested that 80% of events
occurred within 30 days of PCI, with stent thrombosis events numerically less frequent in those
receiving aspirin (randomization was approximately
1 week after PCI) compared with placebo in the
AUGUSTUS (Antithrombotic Therapy After Acute
Coronary Syndrome or PCI in Atrial Fibrillation)
trial.15,16 Therefore, in patients with a high risk of
stent thrombosis, aspirin for up to 30 days after
PCI could be considered. P2Y12 inhibitor therapy
should be continued for at least 12 months after
PCI following aspirin discontinuation but could be
discontinued earlier in those with multiple risk factors for bleeding.17,18
11.2. Reassessment of Lipid Levels
Postdischarge
Recommendation for Reassessment of Lipid Levels Postdischarge
COR
LOE
Recommendation
1
C-LD
1. In patients after ACS, a fasting lipid panel is
recommended 4 to 8 weeks after initiation or
dose adjustment of lipid-lowering therapy to
assess response or adherence to therapy.*1,2
*Modified from the “2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/
AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol.”3
Synopsis
Aggressive LDL-C lowering is an important component of
secondary CVD prevention. For every 1.0-mmol/L (∼39
mg/dL) reduction of LDL-C, an approximate 22% relative
reduction in cardiovascular events is observed over a period of 4 to 5 years.2 Despite the growing number of lipide60
TBD TBD, 2025
lowering therapies currently available, many patients with
ACS do not achieve target LDL-C levels.4,5 The reasons
are varied but include underprescribing by providers, cost
or insufficient coverage by medical insurance companies,
and intolerance to therapies. Many patients are also unwilling or unable to readily fill prescriptions at pharmacies or patients self-discontinue therapy early. Providers
are not always aware of the barriers that patients may be
experiencing; therefore, a conversation between clinician
and patient is important to help improve adherence. If adverse effects are experienced, consideration should be
given to subsequent rechallenge at each visit or changing to a different type of statin or class of lipid-lowering
therapy. Statin intolerance requires exposure to at least
2 different statins with 1 prescribed at the lowest available dose. Because risk of MACE is elevated in the early
months after ACS, early follow-up visits are important
for making appropriate changes to lipid-lowering therapy to help achieve desired LDL-C targets (Section 4.5,
“Lipid Management”). Importantly, lipid-lowering therapies
should not be downtitrated in response to very low LDL-C
concentrations, because current evidence supports that
those with very low LDL-C concentrations are at lowest
risk of MACE without any clear safety concern.6–9
Recommendation-Specific Supportive Text
1. Use of high-potency statin therapy has been
shown to reduce MACE with the benefit appearing
early after ACS and persisting with time.10 To date,
evidence suggests the benefit of lowering LDL-C
concentrations may be irrespective of whether it
is achieved through high-potency statins or other
lipid-lowering therapies; however, the largest body
of evidence exists with statin therapies. As such,
early intensification of lipid-lowering therapy after
ACS is justified. In clinical practice, statin-eligible
patients remain undertreated or untreated.1,11
Early and frequent follow-up, including lipid testing, is associated with improved adherence to
lipid-lowering therapies.1 In the PALM (Provider
Assessment of Lipid Management) registry, less
than one-half of adults were on the statin intensity
recommended by the guidelines.12 In a study of US
veterans with a history of ACS or coronary revascularization, less than one-half of patients received
intensification of lipid-lowering therapy (41.9% at
3 months versus 47.3% at 1-year postdischarge).5
High patient copays and poor coverage of newer
lipid-lowering therapies by some prescription plans
are factors contributing to suboptimal LDL target
attainment. To that end, out-of-pocket costs should
be verified and discussed with patients before they
fill a prescription for a new lipid-lowering therapy.
Education about the importance of lipid-lowering
therapies should be discussed with patients at
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2025 Acute Coronary Syndromes Guideline
11.3. SGLT-2 Inhibitors and GLP-1 Receptor
Agonists
Synopsis
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The cardiovascular benefits of both sodium glucose
cotransporter-2 (SGLT-2) inhibitors and glucagon-like
peptide-1 (GLP-1) receptor agonists are well documented in stable patients with ASCVD and type 2 diabetes,1–6
as well as in patients with HF regardless of diabetes status.7–11 GLP-1 receptor agonists may lead to weight loss
in many patients, and semaglutide has been shown to
reduce the risk of MACE in overweight or obese patients
with stable ASCVD but has not been studied early after
ACS.12 SGLT-2 inhibitors may increase the risk of urinary
tract infection, genital mycotic infection, hypovolemia,
and acute kidney injury (while offering longer term renal
benefit in patients with diabetes). Due to a higher risk of
diabetic and euglycemic ketoacidosis in the perioperative period, canagliflozin, dapagliflozin, and empagliflozin
should be stopped ≥3 days and ertugliflozin ≥4 days prior
to scheduled surgery, including CABG.13–15
The efficacy and safety of SGLT-2 inhibitors have
now been studied in 2 large trials of patients after MI.
In patients without diabetes or HF, dapagliflozin was
not shown to reduce the risk of cardiovascular death or
HF hospitalization in patients with AMI and impaired LV
systolic function.16 Similarly, empagliflozin did not significantly reduce all-cause death or first HF hospitalization in
patients without prior HF who were hospitalized with AMI
and found to have impaired LV systolic function with or
without signs of congestion. However, empagliflozin did
reduce HF hospitalizations in this population.17 No new
safety concerns were identified. Therefore, use of an
SGLT-2 inhibitor does not need to be deferred in patients
with an indication for its use at hospital discharge.
11.4. Use of Chronic Colchicine
Recommendation for Use of Chronic Colchicine
Referenced studies that support recommendation are summarized in
the Evidence Table.
COR
LOE
Recommendation
2b
B-R
1. In patients after ACS, low-dose colchicine may
be reasonable to reduce risk of MACE.1–5
Synopsis
Colchicine is a botanical-derived anti-inflammatory agent
that has been used for millennia in the treatment of gout.
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Colchicine reduces neutrophil adhesion to endothelial
cells and platelets and has been shown to reduce highsensitivity C-reactive protein concentration and low-attenuation plaque volume in patients already on aspirin
and statin therapy.6–9 Colchicine is associated with a
lower risk of MI in patients with gout, as well as in patients with CAD, including those with prior MI.1,4,5,10,11 Although gastrointestinal events were historically reported
at a higher rate in patients on colchicine, this rate does
not differ from placebo at the lower once daily dosing.5 A
meta-analysis of the studies examining colchicine in patients with CAD reported no difference in all-cause death
with colchicine versus placebo, but a nonsignificant trend
was observed toward an increased risk of noncardiovascular death that requires further study.5 To date, no potential pathogeneses of the noncardiovascular deaths
have been consistently shown to explain the numerical
differences in noncardiovascular death.5
Recommendation-Specific Supportive Text
1. COLCOT (Colchicine Cardiovascular Outcomes
Trial) randomized patients ≤30 days (median, 14
days) after MI to low-dose colchicine versus placebo.2 Colchicine reduced the primary outcome of
cardiovascular death, resuscitated cardiac arrest,
MI, stroke, or urgent coronary revascularization by
32% (median follow-up, 22.6 months). Although
directional consistency was seen across individual
components, this benefit was driven by a reduction
in hospitalizations for angina requiring revascularization and stroke. The smaller COPS (Colchicine in
Patients With ACS) study randomized patients during their index hospitalization of ACS to colchicine
versus placebo.3 The primary endpoint of all-cause
death, ACS, unplanned ischemia-driven urgent
revascularization, and noncardioembolic ischemic
stroke was numerically, but not significantly, lower
for patients on colchicine (P =0.09). Although
deaths were infrequent, more deaths occurred for
patients on colchicine than on placebo (8 versus 1;
P =0.017) due to more noncardiovascular deaths.
In a post hoc analysis, the composite outcome
of cardiovascular death, ACS, stroke, or urgent
revascularization was lower for colchicine than placebo. The LoDoCo2 (Low-Dose Colchicine-2) trial
enrolled patients with stable (>6 months) coronary
disease, demonstrating a reduction in the composite of cardiovascular death, MI, ischemic stroke, or
ischemia-driven coronary revascularization with
colchicine (median follow-up, 28.6 months); findings were consistent in the 84% of patients with
prior ACS.4,12 Pooled data from these large trials confirmed a reduction in the incidence of
MACE with colchicine versus placebo.5 Colchicine
should not be administered in patients with blood
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visits to allow them the opportunity to ask questions and review potential barriers. For the management of lipid-lowering therapy initiated prior to
discharge and continued after hospital discharge,
refer to Section 4.5, “Lipid Management.”
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2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
dyscrasias, renal failure (creatinine clearance <15
mL/min), severe hepatic impairment, or with concomitant P-glycoprotein and/or strong CYP3A4
inhibitors. Although the trials studied a dose of 0.5
mg daily, daily dosing of 0.5 mg or 0.6 mg may be
considered. There are ongoing trials studying the
efficacy of colchicine in patients after MI.
11.5. Immunization
Recommendation for Immunization
Referenced studies that support recommendation are summarized in
the Evidence Table.
COR
LOE
Recommendation
1
A
1. In patients with ACS without a contraindication,
annual influenza vaccination is recommended to
reduce the risk of death and MACE.1–4
Synopsis
Downloaded from http://ahajournals.org by on February 28, 2025
Influenza infection is associated with increased risks of
cardiovascular morbidity and mortality.5 Previous studies
have shown that influenza infection may contribute to
atherogenesis and plaque destabilization, thereby precipitating the occurrence of ACS.6,7 Influenza vaccine
has been shown to reduce the risk of death and MACE
in patients after ACS and ASCVD and should therefore
be administered in patients without contraindication.1–3,5,8
Other illnesses such as COVID-19 and pneumococcal
pneumonia increase risk of cardiovascular events and
death in patients with ASCVD. However, randomized
trial data are lacking to support routine administration of
other vaccines for patients at time of hospitalization for
ACS. As such, regular immunization schedules are supported for all patients per the US Centers for Disease
Control and Prevention recommendations in the absence
of contraindication.9
Recommendation-Specific Supportive Text
1. In the FLUVACS (Flu Vaccination in Acute
Coronary Syndromes and Planned Percutaneous
Coronary Interventions) study, cardiovascular death
was lower in patients who received influenza vaccination compared with the control group at both
6-month (2% versus 8%) and 1-year follow-up
(6% versus 17%). The triple composite endpoint of
cardiovascular death, nonfatal MI, and rehospitalization for severe recurrent ischemia at 1 year was
significantly lower in the vaccine group compared
with controls.2,10 Among patients admitted with MI
or high-risk coronary heart disease, influenza vaccine administered within 72 hours of an invasive
coronary procedure or hospitalization resulted in a
lower risk of the composite primary outcome of allcause death, MI, or stent thrombosis and a lower
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risk of cardiovascular death compared with placebo at 1 year.1
12. EVIDENCE GAPS AND FUTURE
DIRECTIONS
The treatment of ACS has been the subject of thousands of clinical trials comprising very large numbers of
patients. As such, its management is guided by the largest evidence base in clinical medicine. Despite this, there
are numerous unanswered questions, evidence gaps,
and areas for further study. Some of these areas have
been addressed by observational studies but were not included in this guideline because the LOE was insufficient
to guide clinical practice. Other areas were not included
because they are less well defined and require more detailed study. This section summarizes some higher priority evidence gaps and areas for future study.
INITIAL EVALUATION AND MANAGEMENT
Although the 2025 ACS guideline recognizes the value
of risk scores in estimating the risk of death or recurrent
MI, limited prospective randomized data are available as
to whether risk scores should be used to determine treatment strategies. The highest risk patients are those who
present after a cardiac arrest. Although the data support
an invasive approach in patients who have been resuscitated and who have evidence of ST-segment elevation
on the postarrest ECG, any potential benefit of coronary
angiography may be attenuated in those who are comatose. Similarly, it is less clear whether reperfusion with
either fibrinolysis or primary PCI provides clinical benefit
in patients with ST-segment elevation who present late
after symptom onset (12 to 48 hours) but who are no
longer symptomatic. Further research is needed to define
the role of coronary angiography and revascularization in
these patient subgroups.
In-Hospital Management of ACS
Patients with ACS are placed on telemetry to monitor
for life-threatening arrhythmias or for rhythm disturbances that may require further therapy (eg, atrioventricular
block, AF). Given the length of stay for most patients with
ACS has decreased significantly, the optimal duration of
telemetry monitoring with contemporary management is
unclear. The increasingly rapid triage and timing of invasive risk stratification also calls into question the value of
“preloading” of oral P2Y12 inhibitors, with preloading defined as administering the loading dose prior to coronary
angiography. As outlined in this document, clinical trials
of preloading have not shown a compelling benefit when
coronary angiography occurs rapidly after the patient’s
clinical presentation. Nonetheless, the pharmacodynamic
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DISCHARGE STRATEGIES AND
SECONDARY PREVENTION
One of the most important areas needing further clarification is the timeline defining the transition of a patient
from ACS to chronic coronary syndrome. The 2025 ACS
guideline does not define this largely because no data
exist to guide any recommendations. Moreover, it is likely
that this transition is highly individualized and accounts for
the patient’s risk at initial presentation, the status of residual unrevascularized CAD, control of cardiovascular risk
factors, and bleeding risk with continued antithrombotic
therapy. Once a patient is deemed to have transitioned
to having a “chronic coronary syndrome,” the question of
how to or whether to de-escalate antiplatelet therapies
is unclear. These decisions may also be influenced by
complications of ACS requiring additional antithrombotic
therapy such as LV thrombus from a large anterior wall
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MI. The role of DOACs in this setting appears prudent
but is not supported by a robust body of data. Other complications such as post-MI pericarditis now have several
therapeutic options, but no comparative data are available
to help determine which approach is optimal.
With respect to long-term secondary prevention, more
research is needed to determine whether home-based
CR provides the same benefit as facility-based programs
and results in higher rates of adherence. Randomized
trials of GLP-1 receptor agonists post MI will be important to understand the role of these agents in reducing
long-term risk in patients with diabetes or those who are
overweight or with obesity. Finally, data are lacking on the
use of high-dose aspirin in those with post-MI pericarditis, and additional data would be useful to confirm the
efficacy of colchicine post ACS.
PEER REVIEW COMMITTEE MEMBERS
Hani Jneid, MD, FACC, FAHA, FSCAI, Chair; Craig J.
Beavers, PharmD, FACC, FAHA; Theresa Beckie, PhD,
RN, FAHA; Jim Blankenship, MD, MACC; Deborah Diercks, MD, FACC; Bruce Lo, MD*; Clauden Louis, MD,
FACC; Faisal M. Merchant, MD, FACC; Noreen Nazir, MD,
FACC; Derek So, MD, MSc, FACC; Matthew Tomey, MD,
FACC, FAHA, FSCAI; Frederick Welt, MD, FACC†
ACC/AHA JOINT COMMITTEE ON CLINICAL
PRACTICE GUIDELINES MEMBERS
Catherine M. Otto, MD, FACC, FAHA, Chair; Sunil V. Rao,
MD, FACC, FSCAI, Chair-Elect; Joshua A. Beckman, MD,
MS, FAHA, FACC, Immediate Past Chair‡; Anastasia
Armbruster, PharmD, FACC; Vanessa Blumer, MD, FACC;
Leslie L. Davis, PhD, RN, ANP-BC, FACC, FAHA; Lisa de
las Fuentes, MD, MS, FAHA‡; Anita Deswal, MD, MPH,
FACC, FAHA‡; Victor A. Ferrari, MD, FACC; Stephen E.
Fremes, MD, FACC; Mario Gaudino, MD, FACC, FAHA;
Adrian F. Hernandez, MD, FAHA‡; Hani Jneid, MD, FACC,
FAHA; Heather M. Johnson, MD, MS, FACC, FAHA; W.
Schuyler Jones, MD, FACC; Sadiya S. Khan, MD, MSc,
FACC, FAHA; Prateeti Khazanie, MD, FAHA‡; Michelle
M. Kittleson, MD, FACC, FAHA; Venu Menon, MD, FACC,
FAHA; Debabrata Mukherjee, MD, MS, FACC, FAHA,
MSCAI; Latha Palaniappan, MD, MS, FACC, FAHA‡;
Tanveer Rab, MD, FACC, MSCAI‡; Garima Sharma, MBBS,
FACC, FAHA; Daichi Shimbo, MD; Jacqueline E. TamisHolland, MD, FACC, FAHA, FSCAI‡; Y. Joseph Woo, MD,
FACC, FAHA‡; Boback Ziaeian, MD, PhD, FACC, FAHA
*American College of Emergency Physicians representative
†Society for Cardiovascular Angiography and Interventions representative.
‡Former ACC/AHA Joint Committee on Clinical Practice Guidelines member;
current member during this writing effort.
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effects of clopidogrel are delayed due to its need to be
metabolized to its active metabolite, and there are reports that the antiplatelet effects of all P2Y12 inhibitors
may be delayed in patients with STEMI. In this context,
parenteral P2Y12 inhibition could be considered but has
not yet been compared to a strategy of more potent oral
P2Y12 inhibitor administration. Other drug therapies in
need of further evaluation in the ACS setting include
the utility of sacubitril-valsartan, nonstatin lipid-lowering
therapies (including clinical outcome studies for PCSK9
inhibitors early after ACS), and GLP-1 receptor agonists
for reducing short- and long-term MACE after ACS. The
clinical benefit of beta blockers in the setting of patients
with NSTE-ACS requires further study, as well as the optimal duration of their use after ACS.
For patients with MVD found during coronary angiography, there are several remaining gaps in evidence. In
patients with NSTEMI, the role of multivessel PCI versus
culprit-only PCI needs further supportive data. As a corollary, whether multivessel PCI in the ACS setting should
be guided by angiography or physiology is still a matter
of debate. Finally, as noted in this guideline, the recommendations for PCI of nonculprit arteries in patients with
STEMI are for patients who are not intended for CABG,
which is a qualifier based on the inclusion criteria of the
randomized trials. The optimal strategy for patients who
have more complex anatomy is less clear.
The 2025 ACS guideline includes a new recommendation regarding the management of cardiogenic shock
using the microaxial flow pump MCS device. Because
the benefit of this device was offset by an increase in
serious complications, more data are needed to guide
the selection of patients for MCS, the timing of MCS
placement and duration of support, and strategies to
reduce the risks of vascular complications, bleeding, and
limb ischemia.
2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
Rao et al
PRESIDENTS AND STAFF
American College of Cardiology
Cathleen Biga, MSN, FACC, President
Cathleen C. Gates, Chief Executive Officer
Richard J. Kovacs, MD, MACC, Chief Medical Officer
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Guidelines
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Leah Patterson, Project Manager, Clinical Content Development
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Heart Association
Thomas S.D. Getchius, National Senior Director, Guidelines
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Methodology
American Heart Association
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Nancy Brown, Chief Executive Officer
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Officer
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of Science Strategies and Operations
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Office of Science and Medicine
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Office of Science and Medicine
Jody Hundley, Senior Production and Operations
Manager, Scientific Publications, Office of Science
Operations
ARTICLE INFORMATION
This document was approved by the American College of Cardiology Clinical Policy Approval Committee and the American Heart Association Science Advisory
and Coordinating Committee in October 2024, the American College of Cardiology Science and Quality Committee in October 2024, and the American Heart
Association Executive Committee in November 2024.
Supplemental materials are available with this article at https://www.ahajournals.org/doi/suppl/10.1161/CIR.0000000000001309
This article has been copublished in the Journal of the American College of
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2025 Acute Coronary Syndromes Guideline
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2.1. Definition and Classification of ACS
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angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J
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3.1.2. Initial In-Hospital Assessment of Patients With
Confirmed or Suspected ACS
1. Diercks DB, Peacock WF, Hiestand BC, et al. Frequency and consequences
of recording an electrocardiogram >10 minutes after arrival in an emergency room in non-ST-segment elevation acute coronary syndromes (from
the CRUSADE Initiative). Am J Cardiol. 2006;97:437–442.
2. Diercks DB, Kontos MC, Chen AY, et al. Utilization and impact of prehospital electrocardiograms for patients with acute ST-segment elevation
myocardial infarction: data from the NCDR (National Cardiovascular Data
Registry) ACTION (Acute Coronary Treatment and Intervention Outcomes
Network) Registry. J Am Coll Cardiol. 2009;53:161–166.
3. Riley RF, Newby LK, Don CW, et al. Diagnostic time course, treatment, and
in-hospital outcomes for patients with ST-segment elevation myocardial
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gency department patients with possible acute coronary syndrome. J Am
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26. Twerenbold R, Badertscher P, Boeddinghaus J, et al. Effect of the FDA
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4.5. Lipid Management
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11. Thiele H, Akin I, Sandri M, et al. One-year outcomes after PCI strategies in
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22. Parikh SV, de Lemos JA, Jessen ME, et al. Timing of in-hospital coronary
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8.1. Revascularization in ACS With Cardiogenic Shock
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myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med. 1999;341:625–634.
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4. Liakopoulos OJ, Schlachtenberger G, Wendt D, et al. Early clinical outcomes
of surgical myocardial revascularization for acute coronary syndromes complicated by cardiogenic shock: a report from the North-Rhine-Westphalia
Surgical Myocardial Infarction Registry. J Am Heart Assoc. 2019;8:e012049.
5. Thiele H, Akin I, Sandri M, et al. PCI strategies in patients with acute myocardial infarction and cardiogenic shock. N Engl J Med. 2017;377:2419–2432.
6. Thiele H, Akin I, Sandri M, et al. One-year outcomes after PCI strategies in
cardiogenic shock. N Engl J Med. 2018;379:1699–1710.
7. Kolte D, Sardar P, Khera S, et al. Culprit vessel-only versus multivessel percutaneous coronary intervention in patients with cardiogenic shock complicating ST-segment-elevation myocardial infarction: a collaborative metaanalysis. Circ Cardiovasc Interv. 2017;10:e005582.
8. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI
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8.2. MCS in Patients With ACS and Cardiogenic Shock
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1. Moller JE, Engstrom T, Jensen LO, et al. Microaxial flow pump or standard
care in infarct-related cardiogenic shock. N Engl J Med. 2024;390:1382–
1393.
2. Ronco D, Matteucci M, Ravaux JM, et al. Mechanical circulatory support as
a bridge to definitive treatment in post-infarction ventricular septal rupture.
J Am Coll Cardiol Intv. 2021;14:1053–1066.
3. Matteucci M, Fina D, Jiritano F, et al. The use of extracorporeal membrane
oxygenation in the setting of postinfarction mechanical complications: outcome analysis of the Extracorporeal Life Support Organization Registry.
Interact Cardiovasc Thorac Surg. 2020;31:369–374.
4. Elbadawi A, Elgendy IY, Mahmoud K, et al. Temporal trends and outcomes of
mechanical complications in patients with acute myocardial infarction. J Am
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5. Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367:1287–
1296.
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2019;74:2117–2128.
12. Dhruva SS, Ross JS, Mortazavi BJ, et al. Association of use of an intravascular microaxial left ventricular assist device vs intra-aortic balloon pump with
in-hospital mortality and major bleeding among patients with acute myocardial infarction complicated by cardiogenic shock. JAMA. 2020;323:734–745.
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Impella® LP5.0 pump and an intra-aortic balloon pump for cardiogenic
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9.1. Mechanical Complications
1. Ronco D, Matteucci M, Ravaux JM, et al. Mechanical circulatory support as
a bridge to definitive treatment in post-infarction ventricular septal rupture.
J Am Coll Cardiol Intv. 2021;14:1053–1066.
2. Matteucci M, Fina D, Jiritano F, et al. The use of extracorporeal membrane
oxygenation in the setting of postinfarction mechanical complications: outcome analysis of the Extracorporeal Life Support Organization Registry.
Interact Cardiovasc Thorac Surg. 2020;31:369–374.
3. Elbadawi A, Elgendy IY, Mahmoud K, et al. Temporal trends and outcomes of
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22. Slater J, Brown RJ, Antonelli TA, et al. Cardiogenic shock due to cardiac
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9.2. Electrical Complications and Prevention of Sudden
Cardiac Death After ACS
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9.4. Management of LV Thrombus After MI
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10.1. Cardiac Intensive Care Unit
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35. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI
guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical
Practice Guidelines. Circulation. 2022;145:e18–e114.
36. Bittl JA, Baber U, Bradley SM, Wijeysundera DN. Duration of dual antiplatelet therapy: a systematic review for the 2016 ACC/AHA guideline focused
update on duration of dual antiplatelet therapy in patients with coronary
artery disease: a report of the American College of Cardiology/American
Heart Association Task Force on Clinical Practice Guidelines. Circulation.
2016;134:e156–e178.
37. Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371:2155–2166.
38. O’Donoghue ML, Murphy SA, Sabatine MS. The safety and efficacy of aspirin discontinuation on a background of a P2Y12inhibitor in patients after
percutaneous coronary intervention: a systematic review and meta-analysis.
Circulation. 2020;142:538–545.
39. Baber U, Jang Y, Oliva A, et al. Safety and efficacy of ticagrelor monotherapy in patients with acute coronary syndromes undergoing percutaneous
coronary intervention: an individual patient data meta-analysis of TWILIGHT
and TICO randomized trials. Circulation. 2024;149:574–584.
40. Valgimigli M, Gragnano F, Branca M, et al. P2Y12 inhibitor monotherapy or
dual antiplatelet therapy after coronary revascularisation: individual patient
level meta-analysis of randomised controlled trials. BMJ. 2021;373:n1332.
41. Valgimigli M, Gragnano F, Branca M, et al. Ticagrelor or clopidogrel monotherapy vs dual antiplatelet therapy after percutaneous coronary intervention: a systematic review and patient-level meta-analysis. JAMA Cardiol.
2024;9:437–448.
42. Michelson AD, Frelinger AL 3rd, Braunwald E, et al. Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITONTIMI 38 trial. Eur Heart J. 2009;30:1753–1763.
43. Palmerini T, Della Riva D, Benedetto U, et al. Three, six, or twelve months of
dual antiplatelet therapy after DES implantation in patients with or without
acute coronary syndromes: an individual patient data pairwise and network
meta-analysis of six randomized trials and 11 473 patients. Eur Heart J.
2017;38:1034–1043.
44. Natsuaki M, Watanabe H, Morimoto T, et al. An aspirin-free versus dual
antiplatelet strategy for coronary stenting: STOPDAPT-3 randomized trial.
Circulation. 2024;149:585–600.
45. Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol.
2008;51:256–260.
46. Sibbing D, Morath T, Stegherr J, et al. Impact of proton pump inhibitors on
the antiplatelet effects of clopidogrel. Thromb Haemost. 2009;101:714–
719.
47. Gargiulo G, Costa F, Ariotti S, et al. Impact of proton pump inhibitors on
clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet
therapy duration: insights from the PROlonging Dual-antiplatelet treatment
after Grading stent-induced Intimal hyperplasia studY trial. Am Heart J.
2016;174:95–102.
48. O’Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect
and clinical efficacy of clopidogrel and prasugrel with or without a protonpump inhibitor: an analysis of two randomised trials. Lancet. 2009;374:989–
997.
49. Goodman SG, Clare R, Pieper KS, et al. Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor:
e84
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2025 Acute Coronary Syndromes Guideline
insights from the platelet inhibition and patient outcomes trial. Circulation.
2012;125:978–986.
50. Storey RF, Angiolillo DJ, Patil SB, et al. Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary
syndromes: the PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy. J Am Coll Cardiol. 2010;56:1456–1462.
51. Capodanno D, Mehran R, Krucoff MW, et al. Defining strategies of modulation of antiplatelet therapy in patients with coronary artery disease: a
consensus document from the Academic Research Consortium. Circulation.
2023;147:1933–1944.
52. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and
response to clopidogrel. N Engl J Med. 2009;360:354–362.
53. Galli M, Benenati S, Capodanno D, et al. Guided versus standard antiplatelet
therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Lancet. 2021;397:1470–1483.
54. Tavenier AH, Mehran R, Chiarito M, et al. Guided and unguided de-escalation from potent P2Y12 inhibitors among patients with acute coronary syndrome: a meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2022;8:492–
502.
55. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. New Engl J Med. 2015;372:1791–
1800.
56. Smits PC, Frigoli E, Vranckx P, et al. Abbreviated antiplatelet therapy after
coronary stenting in patients with myocardial infarction at high bleeding risk.
J Am Coll Cardiol. 2022;80:1220–1237.
11.1.1. Antiplatelet Therapy in Patients on Anticoagulation
Postdischarge
1. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with
dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377:1513–
1524.
2. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with
atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423–2434.
3. Lopes RD, Heizer G, Aronson R, et al. Antithrombotic therapy after
acute coronary syndrome or PCI in atrial fibrillation. New Engl J Med.
2019;380:1509–1524.
4. Vranckx P, Valgimigli M, Eckardt L, et al. Edoxaban-based versus vitamin K
antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised,
open-label, phase 3b trial. Lancet. 2019;394:1335–1343.
5. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without
aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial.
Lancet. 2013;381:1107–1115.
6. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI
guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical
Practice Guidelines. Circulation. 2022;145:e18–e114.
7. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and
safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383:955–962.
8. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/
NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American Heart Association/American College
of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation.
2023;148:e9–e119.
9. Gargiulo G, Goette A, Tijssen J, et al. Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following
percutaneous coronary intervention: a systematic review and meta-analysis
of non-Vitamin K antagonist oral anticoagulant-based randomized clinical
trials. Eur Heart J. 2019;40:3757–3767.
10. Lopes RD, Hong H, Harskamp RE, et al. Optimal antithrombotic regimens
for patients with atrial fibrillation undergoing percutaneous coronary intervention: an updated network meta-analysis. JAMA Cardiology. 2020;5:582–
589.
11. Capodanno D, Di Maio M, Greco A, et al. Safety and efficacy of double antithrombotic therapy with non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention:
a systematic review and meta-analysis. J Am Heart Assoc. 2020;9:e017212.
12. Gargiulo G, Cannon CP, Gibson CM, et al. Safety and efficacy of double vs.
triple antithrombotic therapy in patients with atrial fibrillation with or without
acute coronary syndrome undergoing percutaneous coronary intervention:
a collaborative meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials. Eur Heart J Cardiovasc Pharmacother.
2021;7:F50–F60.
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
Rao et al
11.2. Reassessment of Lipid Levels Postdischarge
Downloaded from http://ahajournals.org by on February 28, 2025
1. Benner JS, Tierce JC, Ballantyne CM, et al. Follow-up lipid tests and physician visits are associated with improved adherence to statin therapy. Pharmacoeconomics. 2004;22 Suppl 3:13–23.
2. Baigent C, Blackwell L, Emberson J, et al. Cholesterol Treatment Trialists
Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised
trials. Lancet. 2010;376:1670–1681.
3. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/
ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Circulation. 2019;139:e1082–e1143.
4. Ramsaran E, Preusse P, Sundaresan D, et al. Adherence to blood cholesterol treatment guidelines among physicians managing patients with
atherosclerotic cardiovascular disease. Am J Cardiol. 2019;124:169–
175.
5. Zheutlin AR, Derington CG, Herrick JS, et al. Lipid-lowering therapy use and
intensification among United States veterans following myocardial infarction or coronary revascularization between 2015 and 2019. Circ Cardiovasc
Qual Outcomes. 2022;15:e008861.
6. Packard C, Chapman MJ, Sibartie M, et al. Intensive low-density lipoprotein
cholesterol lowering in cardiovascular disease prevention: opportunities and
challenges. Heart. 2021;107:1369–1375.
7. Wiviott SD, Cannon CP, Morrow DA, et al. Can low-density lipoprotein be too
low? The safety and efficacy of achieving very low low-density lipoprotein
with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46:1411–1416.
8. Giugliano RP, Wiviott SD, Blazing MA, et al. Long-term safety and efficacy of achieving very low levels of low-density lipoprotein cholesterol: a prespecified analysis of the IMPROVE-IT trial. JAMA Cardiol.
2017;2:547–555.
9. Giugliano RP, Keech A, Murphy SA, et al. Clinical efficacy and safety of
evolocumab in high-risk patients receiving a statin: secondary analysis
of patients with low LDL cholesterol levels and in those already receiving a maximal-potency statin in a randomized clinical trial. JAMA Cardiol.
2017;2:1385–1391.
10. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate
lipid lowering with statins after acute coronary syndromes. N Engl J Med.
2004;350:1495–1504.
11. Lowenstern AM, Li S, Navar AM, et al. Measurement of low-density lipoprotein cholesterol levels in primary and secondary prevention patients: insights
from the PALM Registry. J Am Heart Assoc. 2018;7:e009251.
12. Navar AM, Wang TY, Li S, et al. Lipid management in contemporary community practice: results from the Provider Assessment of Lipid Management
(PALM) Registry. Am Heart J. 2017;193:84–92.
11.3. SGLT-2 Inhibitors and GLP-1 Receptor Agonists
1. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–
1844.
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
2. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–322.
3. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and
renal events in type 2 diabetes. N Engl J Med. 2017;377:644–657.
4. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347–357.
5. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–
2128.
6. Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N Engl J Med. 2021;385:896–
907.
7. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with
heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995–
2008.
8. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with
empagliflozin in heart failure. N Engl J Med. 2020;383:1413–1424.
9. Petrie MC, Verma S, Docherty KF, et al. Effect of dapagliflozin on worsening
heart failure and cardiovascular death in patients with heart failure with and
without diabetes. JAMA. 2020;323:1353–1368.
10. Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med.
2022;387:1089–1098.
11. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a
preserved ejection fraction. N Engl J Med. 2021;385:1451–1461.
12. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and
cardiovascular outcomes in obesity without diabetes. N Engl J Med.
2023;389:2221–2232.
13. American Society of Anesthesiologists Task Force on Preoperative Fasting. Consensus Based Guidance on Preoperative Management of Patients
(Adults and Children) on Glucagon-like Peptide-1 (GLP-1) Receptor Agonists. Accessed May 9, 2024. https://www.asahq.org/about-asa/newsroom/
news-releases/2023/06/american-society-of-anesthesiologists-consensusbased-guidance-on-preoperative.
14. US Food and Drug Administration. FDA Revises Labels of SGLT2 Inhibitors for Diabetes to Include Warnings About Too Much Acid in the
Blood and Serious Urinary Tract Infections. Accessed May 9, 2024.
https://www.fda.gov/drugs/drug-safety-and-availability/fda-reviseslabels-sglt2-inhibitors-diabetes-include-warnings-about-too-muchacid-blood-and-serious.
15. Thompson A, Fleischmann KE, Smilowitz NR, et al. 2024 AHA/ACC/
ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM guideline for perioperative cardiovascular management for noncardiac surgery: a report of
the American College of Cardiology/American Heart Association Joint
Committee on Clinical Practice Guidelines. Circulation. 2024;150:e351–
e442.
16. James S, Erlinge D, Storey RF, et al. Dapagliflozin in myocardial infarction
without diabetes or heart failure. NEJM Evid. 2024;3:EVIDoa2300286.
17. Butler J, Jones WS, Udell JA, et al. Empagliflozin after acute myocardial
infarction. N Engl J Med. 2024;390:1455–1466.
11.4. Use of Chronic Colchicine
1. Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine
for secondary prevention of cardiovascular disease. J Am Coll Cardiol.
2013;61:404–410.
2. Tardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381:2497–2505.
3. Tong DC, Quinn S, Nasis A, et al. Colchicine in patients with acute coronary syndrome: the Australian COPS randomized clinical trial. Circulation.
2020;142:1890–1900.
4. Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic
coronary disease. N Engl J Med. 2020;383:1838–1847.
5. Fiolet ATL, Opstal TSJ, Mosterd A, et al. Efficacy and safety of low-dose
colchicine in patients with coronary disease: a systematic review and metaanalysis of randomized trials. Eur Heart J. 2021;42:2765–2775.
6. Cronstein BN, Molad Y, Reibman J, et al. Colchicine alters the quantitative
and qualitative display of selectins on endothelial cells and neutrophils. J
Clin Invest. 1995;96:994–1002.
7. Nidorf M, Thompson PL. Effect of colchicine (0.5 mg twice daily) on highsensitivity C-reactive protein independent of aspirin and atorvastatin in
patients with stable coronary artery disease. Am J Cardiol. 2007;99:805–
807.
8. Shah B, Allen N, Harchandani B, et al. Effect of colchicine on plateletplatelet and platelet-leukocyte interactions: a pilot study in healthy subjects.
Inflammation. 2016;39:182–189.
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AND GUIDELINES
13. Galli M, Andreotti F, Porto I, Crea F. Intracranial haemorrhages vs. stent
thromboses with direct oral anticoagulant plus single antiplatelet agent or
triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous coronary intervention/acute coronary syndrome
patients. Europace. 2020;22:538–546.
14. Colleran R, Byrne RA, Ndrepepa G, et al. Antithrombotic therapy with or
without aspirin after percutaneous coronary intervention or acute coronary syndrome in patients taking oral anticoagulation: a meta-analysis and
network analysis of randomized controlled trials. Cardiovasc Revasc Med.
2022;36:99–106.
15. Alexander JH, Wojdyla D, Vora AN, et al. Risk/benefit tradeoff of antithrombotic therapy in patients with atrial fibrillation early and late after an acute
coronary syndrome or percutaneous coronary intervention: insights from
AUGUSTUS. Circulation. 2020;141:1618–1627.
16. Lopes RD, Leonardi S, Wojdyla DM, et al. Stent thrombosis in patients with
atrial fibrillation undergoing coronary stenting in the AUGUSTUS trial. Circulation. 2020;141:781–783.
17. Smits PC, Frigoli E, Tijssen J, et al. Abbreviated antiplatelet therapy in patients at high bleeding risk with or without oral anticoagulant therapy after
coronary stenting: an open-label, randomized, controlled trial. Circulation.
2021;144:1196–1211.
18. Valgimigli M, Frigoli E, Heg D, et al. Dual antiplatelet therapy after PCI in
patients at high bleeding risk. N Engl J Med. 2021;385:1643–1655.
2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
Rao et al
9. Vaidya K, Arnott C, Martinez GJ, et al. Colchicine therapy and plaque stabilization in patients with acute coronary syndrome: a CT coronary angiography
study. J Am Coll Cardiol Img. 2018;11:305–316.
10. Crittenden DB, Lehmann RA, Schneck L, et al. Colchicine use is associated
with decreased prevalence of myocardial infarction in patients with gout. J
Rheumatol. 2012;39:1458–1464.
11. Solomon DH, Liu CC, Kuo IH, et al. Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study
using electronic medical records linked with Medicare claims. Ann Rheum
Dis. 2016;75:1674–1679.
12. Opstal TSJ, Fiolet ATL, van Broekhoven A, et al. Colchicine in patients with
chronic coronary disease in relation to prior acute coronary syndrome. J Am
Coll Cardiol. 2021;78:859–866.
11.5. Immunization
1. Frobert O, Gotberg M, Erlinge D, et al. Influenza vaccination after myocardial
infarction: a randomized, double-blind, placebo-controlled, multicenter trial.
Circulation. 2021;144:1476–1484.
2. Gurfinkel EP, Leon de la Fuente R, Mendiz O, Mautner B. Flu vaccination in
acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) study. Eur Heart J. 2004;25:25–31.
3. Ciszewski A, Bilinska ZT, Brydak LB, et al. Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease:
FLUCAD study. Eur Heart J. 2008;29:1350–1358.
2025 Acute Coronary Syndromes Guideline
4. Phrommintikul A, Kuanprasert S, Wongcharoen W, et al. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. Eur Heart J. 2011;32:1730–1735.
5. Madjid M, Miller CC, Zarubaev VV, et al. Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsy-confirmed
coronary heart disease death: results from 8 years of autopsies in 34 892
subjects. Eur Heart J. 2007;28:1205–1210.
6. Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute
myocardial infarction or death from cardiovascular disease: a systematic
review. Lancet Infect Dis. 2009;9:601–610.
7. Dvorakova A, Poledne R. Influenza: a trigger for acute myocardial infarction.
Atherosclerosis. 2004;172:391.
8. Yedlapati SH, Khan SU, Talluri S, et al. Effects of influenza vaccine on
mortality and cardiovascular outcomes in patients with cardiovascular
disease: a systematic review and meta-analysis. J Am Heart Assoc.
2021;10:e019636.
9. US Department of Health and Human Services. Centers for Disease
Control and Prevention. Recommended adult immunization schedule
for ages 19 years or older. Accessed May 1, 2024. https://www.cdc.
gov/vaccines/schedules/downloads/adult/adult-combined-schedule.
pdf.
10. Gurfinkel EP, de la Fuente RL. Two-year follow-up of the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Registry. Tex Heart Inst J.
2004;31:28–32.
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Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
Rao et al
2025 Acute Coronary Syndromes Guideline
Committee
Member
Speakers
Bureau
Ownership/
Partnership/
Principal
Downloaded from http://ahajournals.org by on February 28, 2025
Employment
Consultant
Sunil V. Rao,
Chair
New York University
Langone Health System—
Professor of Medicine,
Director of Interventional
Cardiology
NOT RELEVANT
• Medpace
None
None
NOT RELEVANT
• NHLBI
• PHRI
NOT RELEVANT
• NHLBI*
None
Michelle L.
O'Donoghue,
Vice Chair
Harvard Medical School—
Associate Professor,
Department of Medicine;
Brigham and Women’s
Hospital—Associate
Physician, Senior
Investigator, TIMI Study
Group, McGillycuddy
Logue Distinguished Chair
in Cardiovascular Medicine
NOT RELEVANT
• Verve Therapeutics
None
None
NOT RELEVANT
• AstraZeneca/
MedImmune
(DSMB)
• Janssen
Pharmaceuticals
(DSMB)
None
None
Marc Ruel, Vice
Chair
University of Ottawa Heart
Institute—Professor, Division of Cardiac Surgery
and Department of Cellular
and Molecular Medicine
RELEVANT
• Edwards
Lifesciences
• Medtronic
• XyloC or
None
None
RELEVANT
• Artivion‡
• Artivion*
• AstraZeneca*
• CryoLife*
• Medtronic‡
• Medtronic*
• PhaseBio*
None
None
John H. Alexander
Duke University School
of Medicine—Professor
of Medicine, Division of
Cardiology
NOT RELEVANT
• Akros
• Antev
• Artivion
• AtriCure
• Curis
• Ferring Pharmaceuticals
• Humacyte
• Janssen Pharmaceuticals
• Novostia
• Portola†
• Teikoku Pharma
• Veralox
None
None
NOT RELEVANT
• AbbVie (DSMB)
• AtriCure (DSMB)
• Eli Lilly/Duke
University (DMC)
• FDA†
• Ferring
Pharmaceuticals†
• GlaxoSmithKline
(DSMB)
• NIH‡
• Theravance
(DSMB)
RELEVANT
• Boehringer Ingelheim
None
RELEVANT
• Amgen
• Novartis
Personal Research
Institutional,
Organizational, or
Other Financial Benefit
Expert Witness
RELEVANT
• Amgen†
• AstraZeneca/
MedImmune†
• Merck†
• Novartis†
RELEVANT
• Artivion†
• Bayer†
• Bristol Myers
Squibb†
• CSL Behring†
RELEVANT
• Bayer
• Bristol Myers
Squibb
• Pfizer†
Usman Baber
University of Oklahoma
Health Sciences Center—
Associate Professor of
Medicine
RELEVANT
• Abbott
• Amgen
• AstraZeneca
• Boston Scientific
None
None
None
RELEVANT
• Abiomed*
• Idorsia Pharma*
NOT RELEVANT
• Defendant, heart
failure after acute
MI, 2022
• Defendant, injury
after PCI, 2022
Heather Baker,
Patient
Representative
Dorothy Simon Elementary School—Principal;
Aurora University—Adjunct
Professor
None
None
None
None
NOT RELEVANT
• AHA SFRN‡
None
Mauricio G.
Cohen
Cleveland Clinic Florida—
Director, Structural Heart
Interventions; Staff Physician, Interventional
Cardiology, Heart &
Vascular Center
RELEVANT
• Baylis/Boston
Scientific
• Cordis
None
RELEVANT
• Accumed
Radial
Systems†
RELEVANT
• Abbott
NOT RELEVANT
• SCAI‡
• Abbott*
None
Mercedes CruzRuiz, Patient
Representative
HealthBridge4u—Certified
State Community Health
Worker, Instructor
None
None
None
None
None
None
(Continued )
Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
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e87
CLINICAL STATEMENTS
AND GUIDELINES
Appendix 1. Author Relationships With Industry and Other Entities—2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the
Management of Patients With Acute Coronary Syndromes
Rao et al
2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
Appendix 1. Continued
Committee
Member
Ownership/
Partnership/
Principal
Institutional,
Organizational, or
Other Financial Benefit
Employment
Consultant
Speakers
Bureau
Leslie L. Davis
University of North
Carolina, Chapel Hill—
Associate Professor, PhD
Division, School of Nursing
None
None
None
NOT RELEVANT
• AANP
NOT RELEVANT
• AANP
• ACC
• Elsevier
• Nursing Clinics of
North America
• PCNA
• Sigma Theta Tau
International Honor
Society
• Skin, Bones, Hearts &
Private Parts
• The Journal for Nurse
Practitioners
None
James A. de
Lemos
University of Texas
Southwestern Medical
Center—Professor of
Medicine, Chief of
Cardiology
NOT RELEVANT
• LianBio†
None
None
NOT RELEVANT
• Amgen (DMC)
• AstraZeneca
(DSMB)
• Beckman Coulter
(Endpoint
Committee)†
• Eli Lilly (DSMB)†
• Janssen
Pharmaceuticals
(DSMB)†
• Merck (DSMB)
• Novo Nordisk
(DSMB)†
• Regeneron
(DSMB)
• Siemens (Endpoint
Committee)†
• Varian Medical
Systems (DSMB)
• Verve Therapeutics
(DSMB)
None
None
RELEVANT
• Cytokinetics†
• GlaxoSmithKline†
Personal Research
Expert Witness
Downloaded from http://ahajournals.org by on February 28, 2025
RELEVANT
• Abbott†
• Roche
Diagnostics†
Tracy A.
DeWald
Duke Heart Center—
Clinical Pharmacist and
Assistant Consulting
Professor, Department of
Medicine
NOT RELEVANT
• Bodyport
None
None
NOT RELEVANT
• NHLBI (PI)
NOT RELEVANT
• Cytokinetics‡
• Novartis (Co–PI)*
None
Islam Y. Elgendy
University of Kentucky—
Assistant Professor of
Medicine
None
None
None
None
None
None
Dmitriy N.
Feldman
Weill Cornell Medical
College, New York
Presbyterian Hospital—
Professor of Medicine
None
None
None
None
RELEVANT
• Medtronic*
None
Abhinav Goyal
Emory University School
of Medicine—Professor
of Medicine (Cardiology);
Professor of Epidemiology;
Emory Rollins School
of Public Health—Chief
Quality Officer, Emory
Heart and Vascular Center,
Emory Healthcare
None
None
None
None
None
None
Ijeoma Isiadinso
Emory University School
of Medicine—Associate
Professor of Medicine;
Director of the Emory
Center for Heart Disease
Prevention
None
None
None
None
NOT RELEVANT
• Abbott (DSMB)
• AHA
• Eli Lilly*
• Novartis*
• University of Florida*
None
(Continued )
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Rao et al
2025 Acute Coronary Syndromes Guideline
Appendix 1. Continued
Ownership/
Partnership/
Principal
Institutional,
Organizational, or
Other Financial Benefit
Expert Witness
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Employment
Consultant
Speakers
Bureau
Venu Menon
Cleveland Clinic Lerner
College of Medicine—
Professor of Medicine;
Mehdi Razavi Endowed
Educational Chair; Director
of the Cardiac ICU; Director of the Cardiovascular
Fellowship
None
None
None
NOT RELEVANT
• Edwards
Lifesciences‖
None
None
David A.
Morrow
Harvard Medical School—
Professor of Medicine;
Brigham and Women’s
Hospital—Section Head,
Critical Care Cardiology,
Cardiovascular Division
NOT RELEVANT
• Inflammatix
None
None
NOT RELEVANT
• InCarda (DSMB)
• Softcell†
None
None
Debabrata
Mukherjee
Texas Tech University—
Professor and Chair,
Department of Internal
Medicine, Chief,
Cardiovascular Medicine
NOT RELEVANT
ACC†
None
None
None
NOT RELEVANT
NIH‡
None
Elke Platz
Brigham and Women's
Hospital—Assistant
Professor of Medicine,
Cardiovascular Division;
Harvard Medical School—
Associate Professor of
Emergency Medicine
None
None
None
None
NOT RELEVANT
• AHA†
• Cambridge University
Press
• CVCT Future Clinical
Trialist fellowship
• European Heart
Journal-Acute
Cardiovascular Care‡
• European Journal of
Heart Failure‡
• NIH†
• Women As One‡
None
RELEVANT
• Abbott†
• ARCA Biopharma
• Merck†
• Novartis†
• Regeneron†
• Roche†
Personal Research
CLINICAL STATEMENTS
AND GUIDELINES
Committee
Member
RELEVANT
• Abbott†
• Abiomed†
• Amgen†
• Anthos
Therapeutics†
• ARCA Biopharma†
• AstraZeneca†
• Daiichi Sankyo†
• Eisai†
• GlaxoSmithKline†
• Johnson &
Johnson†
• Merck†
• Novartis†
• Pfizer†
• Regeneron†
• Roche†
• Siemens†
RELEVANT
• AstraZeneca
Susan B.
Promes
Pennsylvania State
University—Professor and
Chair, Department of
Emergency Medicine
None
None
NOT RELEVANT
• ROMTech
None
NOT RELEVANT
• ACEP
• McGraw Hill†
• Penn State University
Department of
Emergency Medicine†
• SAEM†
None
Tanveer Rab
Emory University School
of Medicine—Professor of
Medicine, Interventional
Cardiology
None
None
None
None
NOT RELEVANT
• ABIM
• ACC‡
• Medtronic
• SCAI
None
Sigrid Sandner
Medical University of
Vienna—Associate
Professor of Cardiac
Surgery
None
None
None
None
NOT RELEVANT
• Annals of Thoracic
Surgery, Senior Editor
• Marizyme, Inc.
None
(Continued )
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TBD TBD, 2025
e89
Rao et al
2025 Acute Coronary Syndromes Guideline
CLINICAL STATEMENTS
AND GUIDELINES
Appendix 1. Continued
Committee
Member
Speakers
Bureau
Ownership/
Partnership/
Principal
Employment
Consultant
Yader Sandoval
Minneapolis Heart Institute, Abbott Northwestern
Hospital—Interventional
Cardiologist; Center for
Coronary Artery Disease;
Minneapolis Heart Institute
Foundation—Investigator
RELEVANT
• Abbott†
• GE Healthcare
• Philips†
• Roche†
• Zoll
RELEVANT
• Philips†
• Roche†
NOT RELEVANT
• Patent‡
NOT RELEVANT
• AHRQ (DSMB)
• IFCC Committee
on Clinical
Applications of
Cardiac
Bio-Markers‡
• NHMRC (CEAC)‡
NOT RELEVANT
• JACC: Advances
None
Rachel
Schunder§
AHA/ACC—Science and
Health Advisor, Guidelines
None
None
None
None
NOT RELEVANT
• AHA/ACC salaried
employee
None
Binita Shah
New York University
Grossman School of Medicine—Associate Professor
of Medicine; VA New
York Harbor Healthcare
System—Interventional
Cardiologist
NOT RELEVANT
• Horizons
Therapeutics
• Terumo Medical
None
None
NOT RELEVANT
• CRF (CEC)
• Novo Nordisk†
• The Icahn School
of Medicine at
Mount Sinai (CEC)
NOT RELEVANT
• Abiomed *
• Alleviant*
• Circulation:
Cardiovascular
Interventions†
• Idorsia*
• PHRI*
• SCAI‡
• NHLBI
• VA Office of Research
and Development
None
Wake Forest School of
Medicine—Professor,
Department of Emergency
Medicine
NOT RELEVANT
• Cytovale
None
None
NOT RELEVANT
• AHRQ†
• Comprehensive
Research
Associates, LLC
• Forest Devices
• HRSA†
• The Duke
Endowment†
None
NOT RELEVANT
• Defendant, tendon
injury, 2022
• Plaintiff, pulmonary
embolus, 2022
• Plaintiff, glaucoma,
2023
• Defendant, spinal
compression, 2023
Jason P. Stopyra
RELEVANT
• Boston Scientific
• Philips Volcano†
RELEVANT
• Roche
Personal Research
Institutional,
Organizational, or
Other Financial Benefit
Expert Witness
Downloaded from http://ahajournals.org by on February 28, 2025
RELEVANT
• Abbott
• Chiesi
• Genetesis
• Polymedco
Amy W. Talbot§
AHA/ACC—Science and
Health Advisor, Guidelines
None
None
None
None
NOT RELEVANT
• AHA/ACC salaried
employee
None
Jacqueline E.
Tamis-Holland
Cleveland Clinic—
Interventional Cardiologist
and Institute Director for
Acute Cardiac Care
NOT RELEVANT
• Gaffney Educational Trust
NOT
RELEVANT
• EBIX‡
None
NOT RELEVANT
• PHRI
• Shockwave
Medical‡
NOT RELEVANT
• AHA‡
• Bronx Lebanon Hospital‡
• Concepts Medical*
• Encore Medical
Education
• NYS
• SCAI‡
• Simply K Events
None
Pam R. Taub
University of California at
San Diego—Professor of
Medicine; Director of Step
Family Foundation Cardiac
Rehabilitation and Wellness Center
NOT RELEVANT
• Jazz
Pharmaceuticals†
• Lexicon
Pharmaceuticals
None
NOT RELEVANT
• Epirium Bio†
NOT RELEVANT
• Argenx†
• AtriCure†
• Dexcom
• Regeneron†
NOT RELEVANT
• Milestone
Pharmaceuticals
None
RELEVANT
• Amgen
• Bayer†
• Boehringer
Ingelheim†
• CSL Behring
• Edwards
Lifesciences
• Eli Lilly and
Company†
• Esperion†
• Janssen
Pharmaceuticals‡
• Medtronic
• Novartis†
• Novo Nordisk†
• Sanofi-Aventis
RELEVANT
• Merck
• Novartis†
(Continued )
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Circulation. 2025;151:e00–e00. DOI: 10.1161/CIR.0000000000001309
Rao et al
2025 Acute Coronary Syndromes Guideline
Appendix 1. Continued
Marlene S. Williams
Employment
Consultant
Johns Hopkins Bayview
Medical Center—Clinical
Director of Cardiology and
Associate Professor of
Medicine
NOT RELEVANT
• Haemonetics
Speakers
Bureau
Ownership/
Partnership/
Principal
Personal Research
None
None
None
Institutional,
Organizational, or
Other Financial Benefit
NOT RELEVANT
• Zoll
Expert Witness
None
This table represents all relationships of committee members with industry and other entities that were reported by authors, including those not deemed to be relevant
to this document, at the time this document was under development. The table does not necessarily reflect relationships with industry at the time of publication. A person
is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity, or ownership of
≥$5000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted.
Please refer to https://www.acc.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or
additional information about the ACC/AHA Disclosure Policy for Writing Committees.
*This disclosure was entered under the Clinical Trial Enroller category in the ACC’s disclosure system. To appear in this category, the author acknowledges that there
is no direct or institutional relationship with the trial sponsor as defined in the (ACCF or AHA/ACC) Disclosure Policy for Writing Committees.
†Significant relationship.
‡No financial benefit.
§Rachel Schunder and Amy Talbot are AHA/ACC joint staff members and acted as the Science and Health Advisors for the “2025 ACC/AHA/ACEP/NAEMSP/
SCAI Guideline for the Management of Patients With Acute Coronary Syndromes.” No relevant relationships to report. Nonvoting author on recommendations and not
included/counted in the RWI balance for this committee.
‖The Centers for Medicare & Medicaid Services reported research funding from Edwards Lifesciences to Dr. Menon in 2023 for the ASCEND Study, Commence
Pulmonary Study, and the ViV Surveillance Study, which Dr. Menon disputes.
AANP indicates American Association of Nurse Practitioners; ABIM, American Board of Internal Medicine; ACC, American College of Cardiology; ACCF, American
College of Cardiology Foundation; ACEP, American College of Emergency Physicians; AHA, American Heart Association; AHRQ, Agency for Healthcare Research and
Quality; CEAC, Clinical Events Adjudication Committee; CEC, Clinical Events Committee; CRF, Cardiovascular Research Foundation; CVCT, CardioVascular Clinical Trialists; DMC, Data Monitoring Committee; DSMB, data and safety monitoring board; HRSA, Health Resources and Services Administration; ICU, intensive care unit; IFCC,
International Federation of Clinical Chemistry; JACC, Journal of the American College of Cardiology; MI, myocardial infarction; NHLBI, National Heart, Lung, and Blood
Institute; NAEMSP, National Association of EMS Physicians; NHMRC, National Health and Medical Research Council; NIH, National Institutes of Health; NYS, New York
state; PCI, percutaneous coronary intervention; PCNA, Preventive Cardiovascular Nurses Association; PHRI, Population Health Research Institute; PI, principal investigator; SAEM, Society for Academic Emergency Medicine; SCAI, Society for Cardiovascular Angiography and Interventions; SFRN, Strategically Focused Research Network;
TIMI, Thrombolysis in Myocardial Infarction; and VA, Veterans Affairs.
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e91
CLINICAL STATEMENTS
AND GUIDELINES
Committee
Member
CLINICAL STATEMENTS
AND GUIDELINES
Rao et al
2025 Acute Coronary Syndromes Guideline
Appendix 2. Reviewer Relationships With Industry and Other Entities—2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the
Management of Patients With Acute Coronary Syndromes
Personal
Research
Institutional,
Organizational, or
Other Financial
Benefit
Expert Witness
Downloaded from http://ahajournals.org by on February 28, 2025
Reviewer
Representation
Employment
Consultant
Speakers
Bureau
Ownership/
Partnership/
Principal
Hani Jneid,
Chair
Official
Reviewer—
ACC/AHA Joint
Committee on
Clinical Practice Guidelines
University of Texas Medical
Branch—John Sealy
Distinguished Centennial Chair
in Cardiology; Professor and
Chief, Division of Cardiovascular
Medicine; Medical Director,
Cardiovascular Service Line
None
None
None
None
None
None
Bruce
M. Lo
Organizational
Reviewer—
ACEP
Old Dominion University—
Professor/Assistant Program
Director; Sentara Norfolk
General Hospital—Chief, Department of Emergency Medicine
None
None
None
None
• AAEM
None
Frederick
Welt
Organizational
Reviewer—SCAI
University of Utah— Director,
Cardiac Catheterization
Laboratory
• Faraday
Pharmaceuticals
• Xenter, Inc.
None
None
None
None
• Defendant, perforation during
angioplasty and stent
placement, 2024
• Defendant, death related to
spontaneous bleed, 2024
• Defendant, iatrogenic
dissection of right coronary
artery, 2024
Craig J.
Beavers
Content
Reviewer
University of Kentucky—Assistant
Adjunct Professor
None
None
None
None
None
None
Theresa M.
Beckie
Content
Reviewer
University of South Florida—
Professor
None
None
None
None
None
None
James
Blankenship
Content
Reviewer
University of New Mexico—
Professor; University of New
Mexico Health Sciences—
Director of Cardiac
Catheterization Laboratories
• AMA
• FDA
None
None
None
• ZOLL Medical
None
Deborah
Diercks
Content
Reviewer
UT Southwestern Medical
Center—Professor
• Celecor†
None
None
None
• Abbott Canada
• Emergencies in
Medicine
• Quidel Corp*
• Siemens
• Tosoh
Biomedical*
None
Clauden
Louis
Content
Reviewer
Winter Haven Hospital—Clinical
Associate Physician
None
None
None
None
None
None
Faisal M.
Merchant
Content
Reviewer
Emory University—Director of
Cardiac Electrophysiology
None
None
None
None
• Heart Rhythm
Society
None
Noreen T.
Nazir
Content
Reviewer
University of Illinois at Chicago—
Assistant Professor of Medicine
None
None
None
None
None
None
Derek So
Content
Reviewer
University of Ottawa Heart Institute—Cardiologist
None
None
None
None
None
None
Matthew
Tomey
Content
Reviewer
Mount Sinai Fuster Heart
Hospital—Interventional/
Critical Care Cardiologist
None
None
None
None
• McGraw-Hill
Companies
• AHA
None
This table represents all relationships of reviewers with industry and other entities that were reported at the time of peer review, including those not deemed to be
relevant to this document, at the time this document was under review. The table does not necessarily reflect relationships with industry at the time of publication. A
person is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity, or ownership
of ≥$5000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross income for the
previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise
noted. Names are listed in alphabetical order within each category of review. Please refer to https://www.acc.org/guidelines/about-guidelines-and-clinical-documents/
relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing Committees.
*Significant relationship.
†No financial benefit.
AAEM indicates American Academy of Emergency Medicine; ACC, American College of Cardiology; ACEP, American College of Emergency Physicians; AHA, American Heart Association; AMA, American Medical Association; FDA, US Food and Drug Administration; NAEMSP, National Association of EMS Physicians; SCAI, Society
for Cardiovascular Angiography and Interventions; and UT, University of Texas.
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